The Explained Variance and Discriminant Accuracy of APACHE IVa Severity Scoring in Specific Subgroups of ICU Patients

Robert A Raschke MD^1,2

Richard D Gerkin MD¹

Kenneth S Ramos MD^1,2

Michael Fallon MD²

Steven C Curry MD^1,2

Division of Clinical Data Analytics and Decision Support and the Department of Medicine

University of Arizona College of Medicine-Phoenix.

Phoenix, AZ USA

(Click here for accompanying editorial)

Abstract

Objective: The Acute Physiology and Chronic Health Evaluation (APACHE) is a severity scoring system used to predict healthcare outcomes and make inferences regarding quality of care. APACHE was designed and validated for use in general ICU populations, but its performance in specific subgroups of ICU patients is unproven. Quantitative performance referents for severity scoring systems like APACHE have not been established. This study compares the performance of APACHE IVa in several common subgroups of ICU patients to the performance of APACHE IVa and a referent scoring system applied in a general ICU population.

Design: Observational cohort.

Setting: Seventeen ICUs.

Patients: Adult patients meeting criteria for APACHE IVa scoring.

Intervention: We designed a “two-variable severity score” (2VSS) to provide “weak” reference values for explained variance (R²) and discriminant accuracy to use in our comparisons. R² and AUROC were calculated for 2VSS and APACHE IVa outcome predictions in the overall cohort, and for APACHE IVa in subgroups with sepsis, acute myocardial infarction, coronary artery bypass grafting, stroke, gastrointestinal bleeding, trauma, or requiring mechanical ventilation. APACHE IVa subgroup performance was compared to APACHE VIa and 2VSS performance in the overall cohort.  

Measurements and Main Results: APACHE IVa out-performed 2VSS in our cohort of 66,821 ICU patients (R²: 0.16 vs 0.09; AUROC: 0.89 vs 0.77). However, APACHE IVa performance was significantly diminished in subgroups with sepsis, coronary artery bypass grafting, gastrointestinal bleeding or requiring mechanical ventilation compared to its performance in the overall cohort analysis. APACHE IVa performance in patients undergoing CABG (R²: 0.03, AUROC: 0.74) failed to surpass 2VSS performance referents.

Conclusions:  The performance of severity scoring systems like APACHE might be insufficient to provide valid inferences regarding quality of care in select patient subgroups. Our analysis of 2VSS provides quantitative referents that could be useful in defining acceptable performance.

Introduction

The Acute Physiology and Chronic Health Evaluation (APACHE) has undergone iterative refinement over the past 40 years and is currently the most widely used severity scoring system in the United States (1-3). APACHE provides a score based on the patient’s age, vital signs and laboratory values on the first ICU day and chronic health conditions. This score is used in combination with the patient’s admission diagnosis and other information to calculate predicted hospital and ICU mortality and length-of-stay (LOS), and days of mechanical ventilation. Ratios derived from these calculations, such as the standardized mortality ratio (observed/predicted mortality) and observed/predicted LOS are used by the Centers for Medicare and Medicaid Services, managed care plans, health insurance plans and consumers to benchmark and compare the quality of care provided by physicians, hospitals and healthcare systems. APACHE was updated and revalidated using large clinical databases in 2001-2003, yielding APACHE version IV (1,2) and in 2006-2008, yielding APACHE version IVa (4). 

The use of severity scoring systems such as APACHE to make inferences regarding quality of care is susceptible to bias if the regression models employed do not adequately characterize severity of illness. This is a particular liability when applied to a different population of patients than those for whom the system was originally developed and validated (3,5). This is likely because the optimal set of predictor variables in a severity scoring system is specific to the patient population of interest. The optimal predictor variables for patients with pneumococcal pneumonia might include factors such as prior pneumococcal exposure history, the specific competency of the patient’s immune response against pneumococcus, ciliary function of the lower respiratory tract, current cardiopulmonary capacity, and bacterial virulence factors.  The optimal set of specific predictor variables in patients with stroke or trauma are likely quite different. APACHE uses a set of predictor variables empirically found to be predictive in heterogeneous populations of general ICU patients, but these may not necessarily provide acceptable severity-adjustment for specific subpopulations of ICU patients.

The performance of severity scoring systems is typically assessed using statistical tests that include Pearson’s R-squared (R²) - which describes the “explained variance” of the system for prediction of continuous outcomes like LOS, and the area under the receiver operating curve (AUROC) - which describes the “discriminant accuracy” of the system for prediction of discrete outcomes such as mortality. APACHE IV has yielded an R² of 0.21 for LOS prediction, and AUROC of 0.88 for mortality prediction in a cohort of 131,000 general ICU patients (1,2). However, R² as low as 0.03 and AUROC as low as 0.67 have been reported for APACHE IV outcome predictions in different reference populations, such as those with surgical sepsis (6,7). The performance of the current version, APACHE IVa, is unpublished for many important subgroups of ICU patients.

It has been proposed that AUROC results in the range of 0.70-0.80 indicate “good” discriminant accuracy, and values in the range of 0.80-0.90 are taken to be “very good” or “excellent” (3,8,9), but these subjective ratings have no clear mathematical justification. AUROCs as high as 0.80 have been achieved by scoring systems that utilized only 1-3 predictor variables (10-14). It does not seem plausible that so few variables could acceptably characterize the complex nature of severity-of-illness. R² and AUROC do not have established and well-justified performance thresholds and are therefore of limited value in determining whether a severity scoring system provides valid inferences regarding quality of care.  

Therefore, we first set out to quantify performance thresholds for R² and AUROC by designing a severity score which only incorporated two predictor variables, to intentionally limit the explained variance and discriminant accuracy of the system. This method was previously recommended by the RAND Corporation for assessing severity scoring systems like APACHE because it provides a population-specific referent of unacceptable performance to which the system of interest can be compared (10). We subsequently compared the statistical performance of our two-variable severity score (2VSS) to that of APACHE IVa (which incorporates 142 variables) in a large cohort of ICU patients, and in several common subgroups. Our hypothesis was that APACHE IVa would have diminished and possibly unacceptable explained variance and discriminant accuracy in certain specific subgroups.

Methods

Our Institutional Review Board provided exemption from human research requiring informed consent. Consecutive patients >16 years of age admitted to any ICU in 17 Banner Health acute care hospitals between January 1, 2015 and September 31, 2017 were eligible for inclusion in our cohort of ICU patients. The hospitals ranged from a 44-bed critical access facility to a 708-bed urban teaching hospital in the southwestern United States. The ICUs included general medical-surgical units, as well as specialty-specific cardiovascular, coronary, neurological, transplant and surgical-trauma ICUs. Only the first admission for each patient was included. Patients were excluded if they were admitted as a transfer from another hospital ICU, their ICU LOS was < four hours, or records were missing data required to calculate predicted outcomes using APACHE IVa methodology.

Data used to calculate the acute physiology score (APS) were collected by direct electronic interface between the Cerner Millennium^® electronic medical record and Philips Healthcare Analytics. The worst physiological values occurring during the first ICU day were extracted electronically for Acute Physiology Score (APS) calculation using commercial software provided by the Phillips eICU^® program. Chronic health conditions required for APACHE score calculations and admission information needed for calculation of expected mortality (including admission diagnosis) were entered by nurses who staff our critical care telemedicine service. Observed and predicted ICU and hospital LOS, ventilator days, and ICU and hospital mortality were provided by Philips Healthcare using proprietary APACHE IVa methodology (Cerner Corp. Kansas City, MO).

The 2VSS incorporated only the patient’s age and requirement for mechanical ventilation (yes/no) and used multiple linear regression for prediction of LOS and ventilator days, and multiple logistic regression for prediction of mortality. In contrast, APACHE IVa incorporates 142 variables (27 in the APACHE score, plus 115 admission diagnostic categories) and uses disease-specific regression models serially revised and revalidated in large patient populations (1-3). The two variables incorporated in our 2VSS have been shown to contribute only 10% of the discriminant accuracy of APACHE IV for predicting ICU mortality (1). Therefore, we posited that the best observed AUROC and R² achieved by 2VSS in our cohort analysis could reasonably determine referents of unacceptable performance for comparison with APACHE IVa performance in the analysis of our cohort and in specific subgroups.

Cohort analysis: We used APACHE IVa and the 2VSS to predict five outcomes in our cohort of ICU patients: ICU and hospital LOS, ventilator days, and ICU and hospital mortality. R² was calculated for LOS and ventilator days, and AUROC for mortality outcomes. APACHE IVa results were compared to those of 2VSS. Differences between AUROC results were determined to be statistically significant by comparison of 95% confidence intervals calculated using a nonparametric method based on the Mann-Whitney U-statistic. The highest R² and AUROC achieved by 2VSS in the ICU cohort were used to establish referents of unacceptable performance in all subsequent comparisons.

Subgroup analyses: R² and AUROC were then calculated for APACHE IVa outcome prediction in seven subgroups of ICU patients, including those with admission diagnoses of sepsis, acute myocardial infarction, coronary artery bypass grafting (CABG - with or without other associated cardiac procedures such as valve replacement), stroke, gastrointestinal bleeding, trauma, or requirement of mechanical ventilation. The performance of APACHE IVa in each subgroup was compared to the performance of APACHE IVa and 2VSS in the cohort analysis.

Results

71,094 patients were admitted to study ICUs during the study period. Of these, 2,545 were excluded due to ICU LOS < four hours, 1,379 due to missing data required to calculate APACHE IVa predicted outcomes, and 349 due to transfer from another ICU. The remaining 66,821 patients were included in the analysis. The mean age was 65.7 years (SD 16.3). The most common ICU admission diagnoses were: infections 21.0% (16.8 % due to sepsis); cardiac 14.8% (4.6% due to acute myocardial infarction); cardiothoracic surgery 8.8% (3.8% due to CABG); neurological 8.7% (4.1% due to stroke); pulmonary 7.3%; vascular 5.8%; trauma 5.7%; and gastrointestinal 4.8% (4.0% due to GI bleeds), metabolic/endocrine 4.6%; toxicological 4.5%; cancer 3.8%; and general surgery 3.2%.

Table 1 compares the explained variance (R²) and discriminant accuracy (AUROC) of APACHE IVa and 2VSS outcome predictions in the ICU cohort.

Table 1. Comparison of APACHE IVa to a 2-variable severity score (2VSS) for outcome prediction in a cohort of 66,821 ICU patients. 

Bold font represents the best performance achieved by the 2VSS by R2 and AUROC.

The highest R² achieved by 2VSS was for ICU LOS (R² = 0.09) and the highest AUROC for ICU mortality (AUROC = 0.77).

Subgroup results for APACHE IVa are shown in Table 2.

Table 2. Performance of APACHE IVa outcome prediction in selected subgroups in descending order of discriminant accuracy for ICU mortality. (Click here for enlarged Table 2)

Bold font indicates performance statistically no better than the best performance of 2VSS in the ICU cohort.

*Indicates statistically significantly-reduced performance compared to APACHE IVa in the inclusive ICU cohort (non-overlapping 95% confidence intervals).

Abbreviations: Vent = patients requiring mechanical ventilation; AMI = acute myocardial infarction; GI = gastrointestinal, CABG = coronary artery bypass grafting.

AUROC for APACHE IVa mortality predictions (hospital and ICU mortality) ranged from 0.74-0.90 and were statistically-significantly diminished in subgroups of patients with sepsis, GI bleeds, CABG or mechanical ventilation compared to APACHE IVa performance in the cohort analysis. R² for APACHE IVa prediction of ventilator days was less than 0.09 (the performance referent established by 2VSS) in subgroups of patients with trauma, stroke, acute myocardial infarction, sepsis, GI bleeds and CABG. APACHE IVa predictions of ICU LOS, ventilator days, ICU mortality and hospital mortality for patients who underwent CABG yielded: R² 0.03, R² 0.02, AUROC 0.74 and AUROC 0.75, respectively – all failing to exceed the performance referents established by our cohort analysis by 2VSS.

Discussion

Our study employed empirically-derived, quantitative referents of unacceptable severity-adjustment performance: R² < 0.09 and AUROC < 0.77. APACHE IVa significantly surpassed these referents in all comparisons made in the analysis of our inclusive cohort of ICU patients. R² values for APACHE IVa indicate that it explains about 15- 25% of the variance in hospital and ICU LOS and about 10% of the variance in ventilator days and that it provides discriminant accuracy >0.85 for mortality prediction in this general ICU population. These findings are consistent with previous reports of APACHE IV performance in other large cohorts of ICU patients (1,2,4,15).

However, APACHE IVa performance was significantly diminished in specific subgroups of ICU patients – notably those with sepsis, GI bleeding, requiring mechanical ventilation and undergoing CABG. Values for R² for the prediction of ventilator days in several subgroups were as low as 0.02 – explaining only 2% of the observed variance in ventilator days. Hospital mortality prediction for patients with sepsis yielded an AUROC 0.79 – barely superior to the referent AUROC of 0.77 achieved by 2VSS, and arguably only because of our large sample size. APACHE IVa prediction of ICU LOS, vent days, ICU mortality and hospital mortality in patients undergoing CABG all failed to exceed the performance referents set by 2VSS. 

Few published studies are available to provide meaningful comparisons with the subgroup results from our study. Most describe smaller patient populations outside the U.S. (6,16,17,18). Previous use of APACHE IV to predict outcomes in patients with sepsis reported AUROCs ranging from 0.67 to 0.94 (6,16,19). APACHE IV uses a specific logistic modeling technique and has been specifically validated for CABG patients, but CABG-specific R² and AUROC were not reported (20). No previous study compared APACHE IVa performance in subgroups with that in a general population of ICU patients using quantitative performance referents.

Our findings are important because although general severity scoring systems like APACHE IVa are not optimized for use in specific ICU patient subgroups, they are often used in this manner to make implications regarding quality of care (6,16-19,21-26). In addition to the subgroups discussed above, previous studies have employed general severity scoring system to predict outcomes in subgroups of patients with acute coronary syndrome (17), acute kidney failure (21), malignancy (22), organ transplantation (23), ECMO (24), cardiac surgery (25) and survivors of cardiac arrest (4,26). Many of these studies report AUROCs inferior to our 2VSS referent (6,19,20,23-26). Diagnosis-specific scoring systems, such as the Cardiac Surgery Score (CASUS), generally have provided superior discriminant accuracy in the specific subsets of patients they were designed to serve (27-29).

We believe that general severity scoring systems like APACHE IVa are at an inherent disadvantage in the prediction of outcomes in specific subgroups of ICU patients, because they employ general predictor variables empirically-chosen to work best in heterogeneous patient populations. The APACHE score for example comprises 27 parameters, including vital signs, laboratory values, and specific chronic health items, with a few additional clinical variables added for patients undergoing CABG. As the field of precision medicine has emerged, a rapidly-growing literature describes the use of highly-specific biomarkers, proteomic assays, genomic microarrays and whole-genome sequencing in disease-specific outcome predictions (30-38).  As the science of precision medicine advances, it’s likely that we will develop more precise methods of outcome prediction for specific subgroups of patients that are likely to surpass the performance of general severity scoring systems based only on clinical variables and routine laboratory tests. 

Our study illustrates some features of the explained variance and discriminant accuracy of current severity scoring systems. Our finding that R² does not generally exceed 0.25 is consistent with the findings of other investigators in regards to other well-validated severity scoring systems (2,11,39). This indicates that less than 25% of the between-patient variability in ICU or hospital LOS is explained by current scoring systems. There are two possible explanations for this finding. Either current severity scores are not well-designed to predict LOS, or LOS is inherently not very dependent on severity-of-illness. Our findings imply that ratios of observed/predicted LOS, or observed/predicted ventilator days calculated using current severity scoring systems, may be vulnerable to significant residual bias.  

The differences in the discriminant accuracy achieved by 2VSS and APACHE IVa were surprisingly narrow (e.g., AUROC 0.77 vs. 0.89 for ICU mortality), suggesting that the relationship between AUROC and system complexity is non-linear. We recently performed a Monte Carlo simulation that showed that AUROC increases quadratically in diminishing increments as explanatory power is added to a mortality prediction model, and that the model can achieve an AUROC of 0.85 when only half of important predictor variables have been incorporated (40). This suggests that even the best current severity scoring systems, achieving AUROCs near 0.85, may leave many important aspects of severity-of-illness unaccounted for.

Based on our study results and review of the literature, we suggest that an AUROC ≤ 0.80 represents unacceptable discriminant accuracy in relation to severity scoring systems. This proposition is more conservative than previously-described subjective rating scales (3,8,9), but consistent with published examples of severity scoring systems that are inherently unlikely to yield acceptable discriminant accuracy. Systems incorporating only 1-3 variables have achieved AUROCs of 0.70-0.80, including one intentionally-designed to perform poorly (AUROC 0.70) (10), and others based only on: categorical self-assessment of health (i.e. as poor, good, excellent) (AUROC 0.74) (12), age (AUROC 0.76) (13) or hypotension, tachypnea and altered mentation (AUROC 0.80) (14). Furthermore, a model based only on administrative variables yielded an AUROC 0.81 (41) despite the inaccuracies inherent in such data (42).

Our proposed performance threshold for AUROC implies that organ failure scores, such as the sequential organ failure assessment (SOFA) and the multiple organ dysfunction score (MODS), generally fail to provide acceptable discriminant accuracy (43,44) to mitigate bias in outcome comparisons used to make inferences regarding quality of care.  Outdated versions of severity scoring systems, such as the mortality probability model (MPM) and APACHE II, may achieve discriminant accuracy in the marginal range, with AUROCs of 0.80-0.84 (3,14,45). Well-designed contemporary severity scoring systems, such as APACHE IV, MPM-III, the simplified acute physiology score (SAPS-3), the Veterans Affairs intensive care unit risk adjustment model (1,3,5,9,15,46,47) and several newer machine-learning models (48,49) generally achieve AUROCs ranging from 0.84-0.89 when applied to general patient populations for which they were designed and validated.

Conclusions

Our study suggests that the explained variance and discriminant accuracy of general severity adjustment scoring systems like APACHE might be significantly reduced when they are used to predict outcomes in specific subgroups of ICU patients, and therefore caution should be exercised in making inferences regarding quality of care based on these predictions. Further studies are needed to establish absolute performance criteria for severity scoring systems.

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Acknowledgements

We would like to acknowledge the work of Maria Calleja and Banner Health Clinical Performance Analytics in providing the data used in our analysis.

Author’s contributions

Conception and design: RAR, RDG, KSR, MF, SCC

Data collection: RAR

Statistical analysis: RDG, RAR

Interpretation: RAR, RDG, KSR, MF, SCC

Writing the manuscript: RAR, RDG, KSR, MF, SCC

Guarantor taking full responsibility for integrity of the study: RAR

The authors have no conflicts of interest to report and there was no direct funding for this project.

Abbreviation List

• 2VSS: two-variable scoring system
• APACHE: Acute Physiology and Chronic Health Evaluation
• APS: acute physiology score
• AMI: acute myocardial infarction
• AUROC: area under the receiver operating curve
• CABG: coronary artery bypass grafting
• CASUS: cardiac surgery score
• GI: gastrointestinal
• ICU: intensive care unit
• LOS: length of stay
• MODS: multiple organ dysfunction score
• MPM: mortality probability model
• RAND (corporation): research and development
• R²: Pearson’s coefficient of determination
• SAPS: simplified acute physiology score
• SOFA: sequential organ failure assessment

Cite as: Raschke RA, Gerkin RD, Ramos KS, Fallon M, Curry SC. The explained variance and discriminant accuracy of APACHE IVa severity scoring in specific subgroups of ICU patients. Southwest J Pulm Crit Care. 2018;17:153-64. doi: https://doi.org/10.13175/swjpcc108-18 PDF

Ultrasound for Critical Care Physicians: Characteristic Findings in A Complicated Effusion

Emilio Perez Power MD, Madhav Chopra MD, Sooraj Kumar MD, Tammy Ojo MD, and James Knepler MD

Division of Pulmonary, Allergy, Critical Care and Sleep

University of Arizona College of Medicine

Tucson, AZ USA

Case Presentation

A 60-year-old man with right sided invasive Stage IIB squamous lung carcinoma, presented with a one week history of progressively worsening shortness of breath, fever, and chills. On admission, the patient was hemodynamically stable on 5L nasal cannula with an oxygen saturation at 90%. Physical exam was significant for a cachectic male in moderate respiratory distress using accessory muscles but able to speak in full sentences. His pulmonary exam was significant for severely reduced breath sound on the right along with dullness to percussion. His initial laboratory finding showed a mildly elevated WBC count 15.3 K/mm3, which was neutrophil predominant and initial chest x-ray with complete opacification of the right hemithorax. An ultrasound of the right chest was performed (Figure 1).

Figure 1. Ultrasound of the right chest, mid axillary line, coronal view.

Based on the ultrasound image shown what is the likely cause of the patient’s opacified right hemithorax?

1. Consolidation
2. Exudative pleural effusion
3. Pneumothorax
4. Transudative pleural effusion

Cite as: Power EP, Chopra M, Kumar S, Ojo T, Knepler J. Ultrasound for critical care physicians: characteristic findings in a complicated effusion. Southwest J Pulm Crit Care. 2018;17(6):150-2. doi: https://doi.org/10.13175/swjpcc122-18 PDF

October 2018 Critical Care Case of the Month: A Pain in the Neck

Robert A. Raschke, MD

Critical Care Medicine

HonorHealth Scottsdale Osborn Medical Center

Scottsdale, AZ USA

History of Present Illness

A 54-year-old man was admitted after he had a decline in mental status. He complained of neck and back pain for one week prior to admission for which he took acetaminophen. He was seen in the emergency department two days prior to admission and diagnosed with “arthritis” and prescribed oxycodone/acetaminophen and cyclobenzaprine. On the day of admission be became unresponsive and was transported by ambulance to the emergency department where he was intubated for airway protection.

Past Medical History, Social History, Family History

• Alcoholism
• Hepatitis C
• Esophageal varices
• Family history is noncontributory

Physical Examination

• Vitals: T 102° F, BP 150/60 mm Hg, P 114 beats/min, 20 breaths/min
• Unresponsive
• Dupuytren’s contractures, spider angiomata
• 3/6 systolic murmur
• Deep tendon reflexes 3+  
• Bilateral Babinski’s sign (toes upgoing)

Which of the following are diagnostic considerations at this time? (Click on the correct answer to be directed to the second of six pages)

1. Bacterial endocarditis
2. Hypoglycemia
3. Liver failure
4. 1 and 3
5. All of the above

Cite as: Raschke RA. October 2018 critical care case of the month: a pain in the neck. Southwest J Pulm Crit Care. 2018;17(4):108-13. doi: https://doi.org/10.13175/swjpcc098-18 PDF

Ultrasound for Critical Care Physicians: Who Stole My Patient’s Trachea?

Monika Kakol MD, Connor Trymbulak MSc, and Rodrigo Vazquez Guillamet MD

Department of Internal Medicine Department

University of New Mexico School of Medicine

Albuquerque, NM USA

A 73-year-old man with a past medical history of asthma-chronic obstructive pulmonary disease overlap syndrome and coronary artery disease presented to the emergency department with acute on chronic respiratory failure. The patient failed to respond to initial bronchodilator treatment and non-invasive positive pressure ventilation. A decision was made to proceed with endotracheal intubation and mechanical ventilation. Upper airway ultrasonography was used to confirm positioning of the endotracheal tube and the following images were obtained:

Figure 1. Longitudinal view of the trachea.

Figure 2. Transverse view of the trachea at the level of the tracheal rings.

What does the ultrasound depict (see Figures 1 & 2)? (Click on the correct answer for an explanation)

1. Endotracheal intubation
2. Esophageal intubation
3. Calcified tracheal rings
4. Thyroid

Cite as: Kakol M, Trymbulak C, Guillamet RV. Ultrasound for critical care physicians: Who stole my patient’s trachea? Southwest J Pulm Crit Care. 2018;17(2):72-5. doi: https://doi.org/10.13175/swjpcc102-18 PDF

August 2018 Critical Care Case of the Month

Emma Simpson, MD

Banner University Medical Center Phoenix

Phoenix, AZ USA

History of Present Illness

A 19-year-old gravida 1, para 0 woman in her early second trimester presented to the Emergency Department with intractable vomiting, green sputum icteric sclerae, chest pain, palpitations and weakness for one week prior to presentation. She was visiting the US from an island in Micronesia. The patient has been experiencing feelings of general malaise since the beginning of her pregnancy: she experienced severe nausea and vomiting throughout her first trimester, and a 4.5 kg weight loss in the 2 months prior to presentation.

PMH, SH, FH

Before becoming pregnant, the patient was active and healthy. She does not smoke and her family history is unremarkable.

Physical Examination

Physical exam showed a thin, small young woman. Her physical examination showed a tachycardia of 114 and icteric sclera but was otherwise unremarkable.

Which of the following should be done? (Click on the correct answer to proceed to the second of six pages)

1. Admit to the hospital with measurement of electrolytes, transaminases and bilirubin
2. Discharge to home with a prescription for pyridoxine/doxylamine
3. Ultrasound
4. 1 and 3
5. All of the above

Cite as: Simpson E. August 2018 critical care case of the month. Southwest J Pulm Crit Care. 2018;17(2):53-8. doi: https://doi.org/10.13175/swjpcc092-18 PDF 

Ultrasound for Critical Care Physicians: Caught in the Act

Uzoamaka Ogbonnah MD¹

Isaac Tawil MD²

Trenton C. Wray MD²

Michel Boivin MD¹

¹Department of Internal Medicine

²Department of Emergency Medicine

University of New Mexico School of Medicine

Albuquerque, NM USA

A 16-year-old man was brought to the Emergency Department via ambulance after a fall from significant height. On arrival to the trauma bay, the patient was found to be comatose and hypotensive with a blood pressure of 72/41 mm/Hg. He was immediately intubated, started on norepinephrine drip with intermittent dosing of phenylephrine, and transfused with 3 units of packed red blood cells. He was subsequently found to have extensive fractures involving the skull and vertebrae at cervical and thoracic levels, multi-compartmental intracranial hemorrhages and dissection of the right cervical internal carotid and vertebral arteries. He was transferred to the intensive care unit for further management of hypoxic respiratory failure, neurogenic shock and severe traumatic brain injury. Following admission, the patient continued to deteriorate and was ultimately declared brain dead 3 days later. The patient’s family opted to make him an organ donor

On ICU day 4, one day after declaration of brain death, while awaiting organ procurement, the patient suddenly developed sudden onset of hypoxemia and hypotension while being ventilated. The patient had a previous trans-esophageal echo (TEE) the day prior (Video 1). A repeat bedside TEE was performed revealing the following image (Video 2).

Video 1. Mid-esophageal four chamber view of the right and left ventricle PRIOR to onset of hypoxemia.

Video 2. Mid-esophageal four chamber view of the right and left ventricle AFTER deterioration.

What is the cause of the patient’s sudden respiratory deterioration? (Click on the correct answer to be directed to an explanation)

1. Atrial Myxoma
2. Fat emboli syndrome
3. Thrombus in-transit and pulmonary emboli
4. Tricuspid valve endocarditis

Cite as: Ogbonnah U, Tawil I, Wray TC, Boivin M. Ultrasound for critical care physicians: Caught in the act. Southwest J Pulm Crit Care. 2018;17(1):36-8. doi: https://doi.org/10.13175/swjpcc091-18 PDF 

July 2018 Critical Care Case of the Month

Stephanie Fountain, MD

Banner University Medical Center Phoenix

Phoenix, AZ USA 

History of Present Illness

A 45-year-old man was brought to the Emergency Room by his mother complaining of weakness, dizziness, and trouble swallowing. He was also incontinent of stool and looked “sunburned”.

Past Medical History

He has a past medical history of:

• Schizophrenia
• Depression
• Polysubstance abuse
• Crohn’s disease
• Type 2 diabetes
• Hyperlipidemia

Medications

• Prazosin
• Venlafaxine
• Risperidone
• Buspirone
• Oxcarbazepine
• Gabapentin
• Hydroxyzine
• Lithium
• KCL
• Metformin
• Atorvastatin
• Adalimumab
• Mesalamine
• Prednisone
• Ferrous sulfate

Physical Examination

• Vitals: 80 kg / 97.3 degrees / 101 bpm / 100% 28RR  / BP 111/72 
• The patient was toxic appearing and flushed.
• Oriented to self only, very lethargic
• Dry mucous membranes
• Lungs clear to auscultation and percussion
• Heart tachycardic but no murmurs
• Abdomen without organomegaly, masses or tenderness
• Extremities without edema

Which of the following should be done at this time? (Click on the correct answer to be directed to the second of six pages)

1. Electrolytes
2. Lumbar puncture
3. Urine drug screen
4. 1 and 3
5. All of the above

Cite as: Fountain S. July 2018 critical care case of the month. Southwest J Pulm Crit Care. 2018;17(1):7-14. doi: https://doi.org/10.13175/swjpcc085-18 PDF

June 2018 Critical Care Case of the Month

Stephanie Fountain, MD

Banner University Medical Center Phoenix

Phoenix, AZ USA

History of Present Illness

A 60-year-old native American man presented to an outside hospital with several days of nausea, vomiting and diarrhea. The patient felt weak and called emergency medical services and was taken to the emergency department.

Past Medical History

He has a history of end stage renal disease secondary to diabetes mellitus and hypertension. He received a cadaveric renal transplant in 2008 which was complicated with acute on chronic rejection and symptomatic hyponatremia.

Physical Examination

His pulse was recorded as 28 beats/min and his blood pressure was 90/60.

Which of the following should be done? (Click on the correct answer to be directed to the second of six pages)

1. Administer atropine
2. Begin transcutaneous pacing
3. Obtain a drug history
4. 1 and 3
5. All of the above 

Cite as: Fountain S. June 2018 critical care case of the month. Southwest J Pulm Crit Care. 2018;16(6):304-10. doi: http://doi.org/10.13175/swjpcc065-18 PDF 

Fatal Consequences of Synergistic Anticoagulation

Payal Sen, MD¹

Uddalak Majumdar, MD²

Patrick Rendon, MD¹

Ali Imran Saeed, MD¹

Akshay Sood, MD¹

Michel Boivin, MD¹

¹University of New Mexico

Albuquerque, NM US

²Cleveland Clinic Foundation

Cleveland, OH USA

Abstract

Objective: Novel oral anticoagulants (NOACs) are increasingly being preferred by clinicians (and patients) because they have a wide therapeutic window and therefore do not require monitoring of anticoagulant effect. Herein, we describe the unfortunate case of a patient who had fatal consequences as a result of switching from warfarin to rivaroxaban.

Case Summary: A 90-year-old Caucasian woman, with atrial fibrillation on chronic anticoagulation with warfarin, was admitted to the hospital for pneumonia. She was treated with levofloxacin. In the same admission, her warfarin was switched to rivaroxaban. On Day 3 after the switch, her INR was found to be 6, and she developed a cervical epidural hematoma from C2 to C7. She ultimately developed respiratory arrest, was put on comfort care and died.

Discussion: Rivaroxaban and warfarin are known to have a synergistic anticoagulant effect, usually seen shortly after switching. Antibiotics also increase the effects of warfarin by the inhibition of metabolizing isoenzymes. It is hypothesized that these two effects led to the fatal cervical spinal hematoma. 

Conclusion: The convenience of a wide therapeutic window and no requirement of laboratory monitoring makes the NOACs a desirable option for anticoagulation. However, there is lack of data and recommendations on how to transition patients from Warfarin to NOACs or even how to transition from one NOAC to another. Care should be taken to ensure continuous monitoring of anticoagulation when stopping, interrupting or switching between NOACS to avoid the possibility of fatal bleeding and strokes.

Introduction

Novel oral anticoagulants (NOACs) are increasingly being preferred by clinicians (and patients) because they have a wide therapeutic window and therefore do not require monitoring of anticoagulant effect. They have also shown greater efficacy and safety when compared to warfarin (1). The choice among the novel oral anticoagulants depends on their different pharmacokinetic profile, patients' stroke and bleeding risk, comorbidities, drug tolerability and costs and, finally, patients' preferences (2). There is however, paucity of evidence regarding the process of switching from warfarin to a NOAC, from one NOAC to the other, and the consequent ‘synergism’ (3). Herein, we describe the unfortunate case of a patient who had fatal consequences as a result of switching from warfarin to rivaroxaban. We also wish to highlight the adverse effects that antibiotic interaction can have with both warfarin and the NOACS (4).

Case Report

A 90-year-old Caucasian woman, who resided in a nursing home was admitted to the hospital with chief complaints of fever and confusion for 2 days. She also had intermittent cough, but denied headache, blurry vision, dysuria, diarrhea and constipation. Past medical history was significant for non-valvular atrial fibrillation, for which she was on therapeutic anticoagulation with warfarin. Family history and social history were not significant. Vitals revealed a temperature of 100 F and physical exam was positive for crackles in the right lower lobe of the lung. Her white count was elevated at 16 x 10³/µL, and hepatic and renal function were both normal. Chest x-ray revealed a right sided lower lobe pneumonia. She was admitted to the hospital for acute metabolic encephalopathy due to sepsis secondary to hospital associated pneumonia and was initially given a dose of vancomycin and piperacillin tazobactam, which was later narrowed to levofloxacin. 

Hospital Course

On day 2, the patient’s disorientation had improved marginally and her white count had also reduced to 11. Her INR was therapeutic on warfarin and she underwent transesophageal echocardiography and cardioversion for symptomatic atrial fibrillation with rapid ventricular rate. After a long discussion with the patient and her family, it was decided to switch from warfarin to rivaroxaban, to avoid the hassle of frequent INR monitoring. 

On Day 3, the patient suddenly developed tachypnea, hypotension and dysarthria after receiving the second dose of rivaroxaban. Rapid Response had to be called. Vitals revealed blood pressure of 92/52, respiratory rate 20, and heart rate of 84 with pulse oximetry showing 92% on 2 liters nasal cannula. 

Neurological Examination

Cognition was relatively normal. Patient was alert and oriented X 3.

Motor exam: The patient was quadriplegic.

Touch, pain, and pressure sensations were absent (0/4) below C3-C4.

Reflexes were diminished (¼) and she had absolutely no feeling of any noxious stimuli. Babinsky' s sign was negative.

Urgent Labs on Day 3 (current day)

Arterial blood gases: PaO2 of 62 on 3 liters oxygen via Nasal cannula, PaCO2 of 78.  

International Normalized Ratio (INR): 6, prothrombin time was 64.2 seconds.

Radiographic Imaging

Figure 1. Computed tomography scan of the neck revealed posterior cervical epidural hematoma (arrow) from C2 to C7 with cord compression.

Figure 2. Posterior epidural hematoma (arrow) extending from C2-3 through approximately C6-7, which caused significant spinal stenosis.

The patient was then rushed to the neurosurgical ICU. Neurosurgery was consulted and recommended reversing the anticoagulation and taking the patient for emergency surgical evacuation of the hematoma. However, on further discussion with the family, it was revealed that the patient’s earlier wishes had been to never be bedbound and paralyzed. Since she was a 90-year-old patient, chronically debilitated, with a do not resuscitate code status, the ultimate decision was to place her on comfort care. Patient passed away 24 hours later.

Discussion

Rivaroxaban and warfarin are known to have a synergistic anticoagulant effect, usually seen shortly after switching (5). Antibiotics also increase the effects of warfarin by the inhibition of metabolizing isoenzymes (4). It is hypothesized that these two effects led to the fatal cervical spinal hematoma. 

For decades, vitamin K antagonists like warfarin have been the agent of choice for oral anticoagulation in different clinical conditions. However, the disadvantages of warfarin are that it needs frequent INR monitoring, has a narrow therapeutic window and interacts with multiple food substances and drugs (6). Warfarin is also known to cause major bleeding. The NOACS (novel oral anticoagulants) such as the direct thrombin inhibitor dabigatran, and Factor Xa Inhibitors like rivaroxaban, edoxaban and apixaban have been developed almost fifty years after the approval of warfarin (7). These NOACS have more predictable pharmacodynamics and pharmacokinetics, fewer drug and dietary interactions and have the added advantage of not requiring frequent laboratory monitoring (7,8).  Clinicians are increasingly using these NOACS to replace Vitamin K antagonists for multiple indications like the prevention of thromboembolic complications in atrial fibrillation, treatment of Deep vein thrombosis (DVT) and pulmonary embolism (PE), and thromboprophylaxis during orthopedic surgery (9).

Rivaroxaban, which is an oxazolidinone derivative, inhibits both free Factor Xa and Factor Xa bound in the prothrombinase complex (10). It is a highly selective Factor Xa inhibitor and has high oral bioavailability, with rapid onset of action and a predictable pharmacokinetic profile across a wide spectrum of patients with respect to gender, age, weight and race (11).  There is paucity of data on how to safely switch from warfarin to rivaroxaban. Expert opinion is to switch 24 hours after INR < 3 (3). There is only one observational matched-cohort study of switching from warfarin to rivaroxaban and results supported present practices (3). It analyzed a French registry and fluindidione (not warfarin) was the Vitamin K Antagonist in about 90% of the study subjects. In another study of in silico effects, a post-switch synergistic anticoagulant effect has also been observed and a nomogram has been developed for switching to Rivaroxaban, based on INR for Caucasian and Japanese patients (5). INR is affected variably by rivaroxaban and cannot be used as a marker for its anticoagulant effect (12). Laboratory monitoring of anticoagulant effect of NOACs needs to be considered, since INR is unsuitable for this (13). 

Some of the manufacturers offer guidance relating to switching from warfarin to NOACs:

• To apixaban: warfarin should be discontinued and apixaban started when the INR is <2.0.
• To dabigatran: warfarin should be discontinued and dabigatran started when the INR is <2.0.
• To rivaroxaban: warfarin should be discontinued and rivaroxaban started when the INR is <3.0.

With longer experience with these NOACs in Europe, the European Heart Rhythm Association does make slightly different recommendations than those in the United States (14). Again, looking at switching from a vitamin K antagonist to a NOAC, the group suggests:

• The NOAC can be immediately initiated once the INR is <2.0.
• If the INR is 2.0 to 2.5, the NOAC can be started immediately or (preferably) the next day.
• If the INR is >2.5, use agent pharmacokinetics to estimate the time for the next INR.

As for moving from parenteral anticoagulation to a NOAC, the European recommendation is:

• For unfractionated heparin (UFH), start the NOAC once the UHF is discontinued.
• For low-molecular weight heparin (LMWH), start the NOAC when the next dose of LMWH would have been due.

Hence, switching vitamin K antagonists to newer direct oral anticoagulants (NOACs) is becoming routine now, since the latter are thought to have a reduced incidence of intracranial bleeding (15). This case teaches us that the synergistic effect and interactions with antibiotics should be kept in mind during switching and when possible, nomograms should be used. Further study is required regarding bridging doses, bridging periods and population-specific dosing. 

Conclusion

The convenience of a wide therapeutic window and no requirement of laboratory monitoring makes the NOACs a desirable option for anticoagulation. However, there is lack of data and recommendations on how to transition patients from a vitamin K antagonist to NOACs or even how to transition from one NOAC to another. Care should be taken to ensure continuous monitoring of anticoagulation when stopping, interrupting or switching between NOACS to avoid the possibility of fatal bleeding and strokes. Further trials are also needed to test for appropriate laboratory monitoring of the NOACs. Also, caution must be used whilst using antibiotics with the NOACs, since their interaction can often increase the efficacy of the NOACs and lead to fatal bleeding, like in our patient.

References

1. Prisco D, Cenci C, Silvestri E, Ciucciarelli L, Di Minno G. Novel oral anticoagulants in atrial fibrillation: which novel oral anticoagulant for which patient? J Cardiovasc Med (Hagerstown). 2015 Jul;16(7):512-9. [CrossRef] [PubMed]
2. Gallego P, Roldan V, Lip GY. Novel oral anticoagulants in cardiovascular disease. J Cardiovasc Pharmacol Ther. 2014 Jan;19(1):34-44. [CrossRef] [PubMed]
3. Bouillon K, Bertrand M, Maura G, Blotiere PO, Ricordeau P, Zureik M. Risk of bleeding and arterial thromboembolism in patients with non-valvular atrial fibrillation either maintained on a vitamin K antagonist or switched to a non-vitamin K-antagonist oral anticoagulant: a retrospective, matched-cohort study. Lancet Haematol. 2015 Apr;2(4):e150-9. [CrossRef] [PubMed]
4. Lane MA, Zeringue A, McDonald JR. Serious bleeding events due to warfarin and antibiotic coprescription in a cohort of veterans. Am J Med. 2014 Jul;127(7):657-663.e2. [CrossRef] [PubMed]
5. Burghaus R, Coboeken K, Gaub T, Niederalt C, Sensse A, Siegmund HU, Weiss W, Mueck W, Tanigawa T, Lippert J. Computational investigation of potential dosing schedules for a switch of medication from warfarin to rivaroxaban-an oral, direct Factor Xa inhibitor. Front Physiol. 2014 Nov 7;5:417. [CrossRef] [PubMed]
6. Ezekowitz MD, Aikens TH, Brown A, Ellis Z. The evolving field of stroke prevention in patients with atrial fibrillation. Stroke. 2010 Oct;41(10 Suppl):S17-20. [CrossRef] [PubMed]
7. Mendell J, Zahir H, Matsushima N, Noveck R, Lee F, Chen S, Zhang G, Shi M. Drug-drug interaction studies of cardiovascular drugs involving P-glycoprotein, an efflux transporter, on the pharmacokinetics of edoxaban, an oral factor Xa inhibitor. Am J Cardiovasc Drugs. 2013 Oct;13(5):331-42. [CrossRef] [PubMed]
8. Ogata K, Mendell-Harary J, Tachibana M, Masumoto H, Oguma T, Kojima M, Kunitada S. Clinical safety, tolerability, pharmacokinetics, and pharmacodynamics of the novel factor Xa inhibitor edoxaban in healthy volunteers. J Clin Pharmacol. 2010 Jul;50(7):743-53. [CrossRef] [PubMed]
9. Bauer KA. Recent progress in anticoagulant therapy: oral direct inhibitors of thrombin and factor Xa. J Thromb Haemost. 2011 Jul;9 Suppl 1:12-9. [CrossRef] [PubMed]
10. Roehrig S, Straub A, Pohlmann J, Lampe T, Pernerstorfer J, Schlemmer KH, Reinemer P, Perzborn E. Discovery of the novel antithrombotic agent 5-chloro-N-({(5S)-2-oxo-3- [4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5yl}methyl)thiophene- 2-carboxamide (BAY 59-7939): an oral, direct factor Xa inhibitor. J Med Chem. 2005 Sep 22;48(19):5900-8. [CrossRef] [PubMed]
11. Eriksson BI, Borris LC, Dahl OE, Haas S, Huisman MV, Kakkar AK, Muehlhofer E, Dierig C, Misselwitz F, Kälebo P; ODIXa-HIP Study Investigators. A once-daily, oral, direct Factor Xa inhibitor, rivaroxaban (BAY 59-7939), for thromboprophylaxis after total hip replacement. Circulation. 2006 Nov 28;114(22):2374-81. [CrossRef] [PubMed]
12. Favaloro EJ, Lippi G. The new oral anticoagulants and the future of haemostasis laboratory testing. Biochem Med (Zagreb). 2012;22(3):329-41. [CrossRef] [PubMed]
13. Lindahl TL, Baghaei F, Blixter IF, Gustafsson KM, Stigendal L, Sten-Linder M, Strandberg K, Hillarp A; Expert Group on Coagulation of the External Quality Assurance in Laboratory Medicine in Sweden. Effects of the oral, direct thrombin inhibitor dabigatran on five common coagulation assays. Thromb Haemost. 2011 Feb;105(2):371-8. [CrossRef] [PubMed]
14. Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P; European Heart Rhythm Association. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace. 2013 May;15(5):625-51. [CrossRef] [PubMed]
15. Caldeira D, Barra M, Pinto FJ, Ferreira JJ, Costa J. Intracranial hemorrhage risk with the new oral anticoagulants: a systematic review and meta-analysis. J Neurol. 2015 Mar;262(3):516-22. [CrossRef] [PubMed]

Cite as: Sen P, Majumdar U, Rendon P, Saeed AI, Sood A, Boivin M. Fatal consequences of synergistic anticoagulation. Southwest J Pulm Crit Care. 2018;16(5):289-95. doi: https://doi.org/10.13175/swjpcc058-18 PDF 

May 2018 Critical Care Case of the Month

Lacey Gagnon APRN, CNP
Theo Loftsgard APRN, CNP

Department of Anesthesiology and Critical Care

Mayo Clinic Minnesota

Rochester, MN USA

Chief Complaint

Shortness of breath

History of Present Illness

The patient is a 44-year-old woman who was admitted with a history of “pericarditis”. She has a several years history of progressive shortness of breath, abdominal distention and lower extremity edema.

Past Medical History, Social History and Family History

She has a history of obesity, poorly controlled type 2 diabetes, uterine fibroids and hypertension. She does not smoke but does have 1-2 alcoholic beverages per day. Family history is noncontributory.

Physical Examination

• Vital signs: pulse 96 beats/min, blood pressure 110/85 mm Hg, temperature 37° C, respirations 18 breaths/min.
• Neck: there is jugular venous distention with a positive hepatojugular reflux.
• Lungs: rales at both bases.
• Heart: regular rhythm without murmur.
• Abdomen: Distended. Shifting dullness is present.
• Extremities: 2-3 pretibial pitting edema.

Chest Radiography

Chest x-ray shows a small right pleural effusion with mild vascular congestion at the bases. Heart size is normal.

Which of the following should be performed?

1. Abdominal CT scan
2. Echocardiography
3. Thoracic CT scan
4. 1 and 3
5. All of the above

Cite as: Gagnon L, Loftsgard T. May 2018 critical care case of the month. Southwest J Pulm Crit Care. 2018;16(5):245-51. doi: https://doi.org/10.13175/swjpcc048-18 PDF 

Airway Registry and Training Curriculum Improve Intubation Outcomes in the Intensive Care Unit

Joshua Malo MD¹

Cameron Hypes MD²

Bhupinder Natt MBBS¹

Elaine Cristan MD¹

Jeremy Greenberg MD¹

Katelin Morrissette MD¹

Linda Snyder MD¹

James Knepler MD¹

John Sakles MD²

Kenneth Knox MD¹

Jarrod Mosier MD²

¹ Department of Medicine, University of Arizona College of Medicine, Tucson, AZ

² Department of Emergency Medicine, University of Arizona College of Medicine, Tucson, AZ

Abstract

Background: Intubation in critically ill patients remains a highly morbid procedure, and the optimal approach is unclear. We sought to improve the safety of intubation by implementing a simulation curriculum and monitoring performance with an airway registry. 

Methods and Methods: This is a prospective, single-center observational study of all intubations performed by the medical intensive care unit (ICU) team over a five-year period. All fellows take part in a simulation curriculum to improve airway management performance and minimize complications. An airway registry form is completed immediately after each intubation to capture relevant patient, operator, and procedural data.  

Results: Over a five-year period, the medical ICU team performed 1411 intubations. From Year 1 to Year 5, there were significant increases in first-attempt success (72.6 vs. 88.0%, p<0.001), use of video laryngoscopy (72.3 vs. 93.5%, p<0.001), and use of neuromuscular blocking agents (73.5 vs. 88.4%, p<0.001). There were concurrent decreases in rates of desaturation (25.6 vs. 17.1%, p=0.01) and esophageal intubations (5 vs. 1%, p=0.009). Low rates of hypotension (8.3%) and cardiac arrest (0.6%) were also observed.

Conclusions: The safety of intubation in critically ill patients can be markedly improved through joint implementation of an airway registry and simulation curriculum.

Introduction

Airway management is one of the highest risk procedures that can be performed in the intensive care unit (ICU). Despite technologic advances in methods for performing intubation, recent studies continue to report frequent adverse events associated with tracheal intubation, and complications occur in up to 40% of procedures (1-3). Even in the absence of anatomic predictors of a difficult airway, critically ill patients are particularly vulnerable to desaturation, hemodynamic instability, and cardiac arrest due to poor physiologic reserve (4, 5). Repeated or prolonged intubation attempts exhaust any physiologic reserve these patients may have, leading to more frequent adverse outcomes (6). Thus, maximizing first attempt success without an adverse event is the goal for airway management in this high-risk population (7, 8).

Much of the clinical practice regarding airway management in the ICU has been extrapolated from studies performed during elective intubations in the operating room (4). In recent years, there has been a greater focus on management strategies and outcomes in critically ill patients in the emergency department (ED) and ICU (3, 9, 10). In 2012, we initiated a comprehensive airway management quality improvement program to measure variables related to airway management in the ICU and identify targeted opportunities for intervention to improve outcomes (11). We first established a prospectively collected registry of all intubations performed in the medical ICU. After evaluation of the first year of data, a simulation-based curriculum for the pulmonary and critical care fellows was developed with a focus on identifying high-risk features, minimizing adverse events, and maximizing first-attempt success. Lastly, research questions were evaluated periodically to identify targeted opportunities for improvement. This paper will describe the outcomes after the first 5 years of our program.

Materials and Methods

This is a prospective single-center observational study of all intubations performed in the medical ICU from January 1, 2012 to December 31, 2016. The study has been granted an exemption from full review and is approved by the University of Arizona Institutional Review Board. The primary outcome of interest was first attempt success, while secondary outcomes included adverse events, drug and device selection, and method of preoxygenation.

This study took place at a large academic medical center with 20+ bed medical ICU. A medical ICU team consisting of an attending intensivist, a pulmonary/critical care or emergency medicine/critical care fellow, and internal medicine, emergency medicine, and occasionally family medicine residents assumes primary management of all patients admitted to the medical ICU service. All patients admitted to the ICU undergoing airway management by the medical ICU team were included in the study.

We have maintained a continuous quality improvement (CQI) database for all episodes of airway management performed by our medical intensive care teams since January 1, 2012. After each intubation, the operators record data pertinent to the procedure, including difficult airway characteristics, drug and device selection, and number of attempts, using a standardized form. The study primary investigator crosschecked a report generated by the electronic health record against the database to ensure forms were completed for all intubations. Forms were reviewed for completeness and internal consistency. Inconsistent or absent data were resolved by interview of the operator. The variables captured in the form have been previously described (11) and are adjusted occasionally to evaluate new variables of interest.

Our Pulmonary and Critical Care Medicine (PCCM) and Critical Care Medicine (CCM) fellowship programs implemented an 11-month, simulation-based airway management curriculum beginning on July 1, 2013. The curriculum is designed to improve situational awareness in the peri-intubation period as well as to emphasize techniques that will optimize chances of first-attempt success while minimizing complications. The general outline for the simulations has been previously described in detail (11). Briefly, the curriculum involves clinical scenarios of varying and generally progressive complexity, each of which is meant to emphasize certain aspects of airway management. As trainees progress, the curriculum emphasizes the identification and mitigation of factors that may decrease the likelihood of first-attempt success and increase the likelihood of complications. The annual fellowship complement includes 14 Pulmonary and Critical Care Medicine fellows and 2 Critical Care Medicine fellows. All fellows participate in the curriculum, which is updated to include recent advances in airway management from the literature and analysis of our own airway registry. A debriefing session following each simulation is used to emphasize specific learning points for the approach to airway management.

Statistical Analysis

Descriptive statistics were calculated for measured variables as means and standard deviations, medians and interquartile ranges (IQR), or proportions as appropriate. Categorical variables were compared using Fisher’s exact test. Comparisons between Year 1 and Year 5 were performed using the Two-Sample Test of Proportions. Categorical variables with multiple groups, such as preoxygenation, Operator PGY, and Device were evaluated with the test for trend using the likelihood ratio test. All statistical analyses were performed with Stata Version 14 (StataCorp, College Station, TX).

Results

During the 60-month study period, there were 1411 intubations performed. The patient and operator characteristics are shown in Table 1 and Table 2, respectively.

Table 1. Patient characteristics.

^aSome DACs added over time. Limited mouth opening and secretions added after the first 8 months of data collection.

Table 2. First Operator Characteristics.

During the course of the study, there was no significant change in patient age or gender, the presence of difficult airway characteristics, starting saturation, or percentage of patients intubated after failing noninvasive positive pressure ventilation (NIPPV). There was a trend for decreased intubations resulting from failed extubation. The overall characteristics of intubation attempts are described in Table 3.

Table 3. Intubation characteristics.

There was a significant increase in the number of intubations performed by PCCM operators after the first year of the study (Year 1-5 difference +19%, p<0.001) accompanied by a decrease in intubations performed by internal medicine (Year 1-5 difference -9%, p=0.006) and emergency medicine residents (Year 1-5 difference -10%, p=0.003). Likewise, there was an increase in intubations performed by PGY 4 (Year 1-5 difference +13%, p=0.002) and PGY 6 (Year 1-5 difference +11%, p<0.001) operators with a concurrent decrease in those performed by PGY 2 (Year 1-5 difference -16%, p<0.001) and PGY 3 (Year 1-5 difference -8%, p=0.004) operators.

First-attempt success (FAS) occurred in 80.7% of intubations performed during the study period. The FAS rate increased linearly throughout the study period, with FAS of 72.6% in the first year and 88.0 % in the final year when looking at all operators (p<0.001) (Table 4, Figure 1, next page). 

There was a significant increase in the number of intubations performed by PCCM operators after the first year of the study (Year 1-5 difference +19%, p<0.001) accompanied by a decrease in intubations performed by internal medicine (Year 1-5 difference -9%, p=0.006) and emergency medicine residents (Year 1-5 difference -10%, p=0.003). Likewise, there was an increase in intubations performed by PGY 4 (Year 1-5 difference +13%, p=0.002) and PGY 6 (Year 1-5 difference +11%, p<0.001) operators with a concurrent decrease in those performed by PGY 2 (Year 1-5 difference -16%, p<0.001) and PGY 3 (Year 1-5 difference -8%, p=0.004) operators.

First-attempt success (FAS) occurred in 80.7% of intubations performed during the study period. The FAS rate increased linearly throughout the study period, with FAS of 72.6% in the first year and 88.0 % in the final year when looking at all operators (p<0.001) (Table 4, Figure 1).

Table 4. Outcomes.

Figure 1. First-attempt success and complications over time.

For patients intubated by fellows only, FAS increased from 77% to 92% over the 5-year period (p<0.001).

During the entire study period, at least one complication occurred in 28.7% of intubations. The incidence of complications decreased throughout the first 48 months but increased slightly in the final 12 months of the study, driven primarily by an increase in hypotension (Table 4, Figure 2).

Figure 2. Neuromuscular blocking agent (NMBA) use, video laryngoscopy (VL) use, and occurrence of esophageal intubations, desaturation, and hypotension over time.

There was a decrease in the rate of desaturation from the first year to the final year of the study (25.6% to 17.1%, p=0.01). Esophageal intubations also decreased significantly over this time (5% to 1%, p=0.009). Hypotension and cardiac arrest occurred in 8.3% and 0.6% of intubations, respectively, during the entire study period.

There was a trend towards decreased use of midazolam and propofol throughout the study period while the use of etomidate tended to increase, although these changes were not significant (Table 3). A neuromuscular blocking agent (NMBA) was used in 77.4% of intubations during the study period, increasing from the first year to the final year (73.5% to 88.4%, p<0.001), driven primarily by an increase in the use of rocuronium.

There was a significant transition from the use of direct laryngoscopy (DL) to video laryngoscopy (VL) over the course of the study (p<0.001). DL was chosen as the first approach in 22.0% of intubations in the first year and only 2.9% in the final year. Conversely, the use any form of VL on the first attempt increased from 72.3% of intubations in the first year to 93.5% in the final year. Flexible fiber optic intubation was used infrequently during the entire study period, being the first device used in 4.3% of intubations.

Various methods of preoxygenation were used throughout the study period with some form of preoxygenation occurring in 97.5% of intubations. From the first year to the final year of the study, the use of bag-valve-mask (BVM) ventilation tended to decrease (30% to 12.2%) with a concurrent trend in increasing use of NIPPV for preoxygenation (19.4% to 29.7%).

Discussion

Our experience demonstrates that utilization of a comprehensive approach to airway management including an ongoing simulation-based training curriculum and CQI database is associated with an improved first-attempt success rate for the intubation of critically ill patients. This was accompanied by changes in approach to airway management, with increased use of VL and NMBA on the first attempt, as well as an increased proportion of airways being managed by more experienced operators.

While some of the observed improvement in FAS may be attributed to more experienced operators managing the airway on the first attempt, the sharp increase in fellow-level operators after implementation of the curriculum may point to increased fellow confidence or increased recognition of high-risk patients. Furthermore, as adjunctive strategies such as ramp positioning (12-14) and apneic oxygenation (15, 16) have become increasingly recognized as potentially beneficial, a continuous training curriculum provides opportunities for evaluating trainees’ knowledge of these techniques and reinforcing their incorporation into airway management.

We have previously reported on the impact of a simulation-based curriculum on operator confidence, first-attempt success, and procedural complications (11). The combination of this curriculum with a CQI database has a marked effect on the approach to management of these patients. Strategies presented and employed in the curriculum have been informed by previous reports from our database. For example, after demonstrating improved first-attempt success with the use of neuromuscular blockade (17) and video laryngoscopy (18), the didactic portion of our curriculum incorporated these findings, which were rapidly used with increasing frequency in our intensive care unit. The integration of the curriculum and CQI database facilitates adoption of best practices, leading to a significant improvement of first-attempt success rate over a relatively short time span. The continued improvement over the course of five years is likely due to the incorporation of the practices above during this time.

Tools traditionally used for predicting difficulty of airway management have focused primarily on characteristics of an anatomically difficult intubation (19, 20). More recently, there has been an expanded focus on physiologic characteristics that may lead to complications and decreased success of intubation. However, currently available instruments for ICU patients, such as the MACOCHA score, continue to put heavy emphasis on anatomic factors and are not validated for the use of VL (21). We have found difficult airway characteristics associated with decreased FAS in the setting of VL and have focused efforts at minimizing their impact (22). In our population, we noted a consistent improvement in Cormack-Lehane grade and percentage of glottic opening (POGO) score, despite a high prevalence of anatomic difficult airway characteristics. We have also noted a significant decrease in desaturations, esophageal intubations, and a trend towards decreased overall complications. In comparison to other studies of intubation complications in critically ill patients, we found generally lower rates of esophageal intubation (1, 2, 6) and similar (10) or lower rates of desaturation (1, 2) (Table 5).

Table 5. Incidence of complications in the published literature.

Our rate of hypotension is fairly low relative to several other studies (2, 10, 23) despite a fairly inclusive definition (administration of fluid or phenylephrine bolus, initiation or increase of vasopressor infusion). Moreover, cardiac arrest was extremely uncommon in our population, occurring in 0.57% of intubations.

Data regarding optimal approach have been controversial, and randomized trial results do not always coincide with observational studies. Although randomized controlled trials have called into question the benefit of VL (24-27), there are several important limitations to each of these studies to consider when interpreting the comparison between DL and VL. In some, patients were excluded either directly (25) or indirectly (24, 26) for a history of a difficult intubation or anticipated difficult intubation. The use of endotracheal tubes without a stylet may have also influenced outcomes (27).

Our experience is a pragmatic example of the effect of device selection on first attempt success in that we have >1400 patients, operators with varying experience, and have no patients excluded because of potential difficulty. Thus, while randomized trials may be ideal, they are costly and time-consuming and may delay identification and implementation of best practices. The FAS rate in our cohort in its first year was similar to that observed in several of these trials but improved substantially over the 5-year period. One reason for the improved FAS in our study may be the continuous simulation-based training with a focus on video laryngoscopy as the first technique of choice for the majority of airways. In comparison to other widely cited studies of airway management in critically ill patients (1, 21), our cohort demonstrated a very low incidence of difficult airways, only 2% in the final year, despite a similar presence of difficult airway characteristics. This may be an effect of the training program suggesting that perhaps airway training with a global view of airway management focusing on increasing FAS and reducing complications is even more important than equipment considerations.

Our study has several limitations. The single-center, observational nature of this study makes it at risk of bias despite attempts to identify and control for factors that may influence the results. Data forms were completed by the operator, introducing potential for reporting bias, although attempts to minimize this were made by intermittent correlation with the medical record. Although FAS is an accepted outcome for studies evaluating intubation strategies, data regarding mortality or late morbidity were not captured. The increase in hemodynamic complications in the final year is of interest, but data regarding this complication and its consequences were limited and should be a focus of future research. Despite these limitations, the consistent improvement in FAS and low incidence of difficult airways in the final year of the study warrant serious consideration of these findings.

Conclusion

We have found that a comprehensive strategy employing a simulation-based curriculum and continuous quality improvement database was associated with significant improvements in first-attempt success at intubation in critically ill patients throughout the 5-year study period. We suggest that wider adoption of this practice could vastly improve the safety of intubation in this high-risk patient population.

References

1. Griesdale DE, Bosma TL, Kurth T, Isac G, Chittock DR. Complications of endotracheal intubation in the critically ill. Intensive Care Med. 2008;34(10):1835-42. [CrossRef] [PubMed]
2. Jaber S, Amraoui J, Lefrant JY, Arich C, Cohendy R, Landreau L, et al. Clinical practice and risk factors for immediate complications of endotracheal intubation in the intensive care unit: a prospective, multiple-center study. Crit Care Med. 2006;34(9):2355-61. [CrossRef] [PubMed]
3. Lapinsky SE. Endotracheal intubation in the ICU. Crit Care. 2015;19:258. [CrossRef] [PubMed]
4. Mort TC. The incidence and risk factors for cardiac arrest during emergency tracheal intubation: a justification for incorporating the ASA Guidelines in the remote location. J Clin Anesth. 2004;16(7):508-16. [CrossRef] [PubMed]
5. Mosier JM, Joshi R, Hypes C, Pacheco G, Valenzuela T, Sakles JC. The Physiologically Difficult Airway. West J Emerg Med. 2015;16(7):1109-17. [CrossRef] [PubMed]
6. Mort TC. Emergency tracheal intubation: complications associated with repeated laryngoscopic attempts. Anesth Analg. 2004;99(2):607-13, table of contents.  [CrossRef] [PubMed]
7. Hypes C, Sakles J, Joshi R, Greenberg J, Natt B, Malo J, et al. Failure to achieve first attempt success at intubation using video laryngoscopy is associated with increased complications. Intern Emerg Med. 2017 Dec;12(8):1235-43. [CrossRef] [PubMed]
8. Park L, Zeng I, Brainard A. Systematic review and meta-analysis of first-pass success rates in emergency department intubation: Creating a benchmark for emergency airway care. Emerg Med Australas. 2017;29(1):40-7. [CrossRef] [PubMed]
9. Simpson GD, Ross MJ, McKeown DW, Ray DC. Tracheal intubation in the critically ill: a multi-centre national study of practice and complications. Br J Anaesth. 2012;108(5):792-9. [CrossRef] [PubMed]
10. Smischney NJ, Seisa MO, Heise KJ, Busack KD, Loftsgard TO, Schroeder DR, et al. Practice of Intubation of the Critically Ill at Mayo Clinic. J Intensive Care Med. 2017:885066617691495. [CrossRef] [PubMed]
11. Mosier JM, Malo J, Sakles JC, Hypes CD, Natt B, Snyder L, et al. The impact of a comprehensive airway management training program for pulmonary and critical care medicine fellows. A three-year experience. Ann Am Thorac Soc. 2015;12(4):539-48. [CrossRef] [PubMed]
12. Khandelwal N, Khorsand S, Mitchell SH, Joffe AM. Head-Elevated Patient Positioning Decreases Complications of Emergent Tracheal Intubation in the Ward and Intensive Care Unit. Anesth Analg. 2016;122(4):1101-7. [CrossRef] [PubMed]
13. Ramkumar V, Umesh G, Philip FA. Preoxygenation with 20 masculine head-up tilt provides longer duration of non-hypoxic apnea than conventional preoxygenation in non-obese healthy adults. J Anesth. 2011;25(2):189-94. [CrossRef] [PubMed]
14. Turner JS, Ellender TJ, Okonkwo ER, Stepsis TM, Stevens AC, Sembroski EG, et al. Feasibility of upright patient positioning and intubation success rates at two academic emergency departments. Am J Emerg Med. 2017. [CrossRef] [PubMed]
15. Mosier JM, Hypes CD, Sakles JC. Understanding preoxygenation and apneic oxygenation during intubation in the critically ill. Intensive Care Med. 2017;43(2):226-8. [CrossRef] [PubMed]
16. Sakles JC, Mosier JM, Patanwala AE, Arcaris B, Dicken JM. First Pass Success Without Hypoxemia Is Increased With the Use of Apneic Oxygenation During Rapid Sequence Intubation in the Emergency Department. Acad Emerg Med. 2016;23(6):703-10. [CrossRef] [PubMed]
17. Mosier JM, Sakles JC, Stolz U, Hypes CD, Chopra H, Malo J, et al. Neuromuscular blockade improves first-attempt success for intubation in the intensive care unit. A propensity matched analysis. Ann Am Thorac Soc. 2015;12(5):734-41. [CrossRef] [PubMed]
18. Hypes CD, Stolz U, Sakles JC, Joshi RR, Natt B, Malo J, et al. Video Laryngoscopy Improves Odds of first-attempt success at intubation in the intensive care unit. A propensity-matched analysis. Ann Am Thorac Soc. 2016;13(3):382-90. [CrossRef] [PubMed]
19. Mallampati SR, Gatt SP, Gugino LD, Desai SP, Waraksa B, Freiberger D, et al. A clinical sign to predict difficult tracheal intubation: a prospective study. Can Anaesth Soc J. 1985;32(4):429-34. [CrossRef] [PubMed]
20. Wilson ME, Spiegelhalter D, Robertson JA, Lesser P. Predicting difficult intubation. Br J Anaesth. 1988;61(2):211-6. [CrossRef] [PubMed]
21. De Jong A, Molinari N, Terzi N, Mongardon N, Arnal JM, Guitton C, et al. Early identification of patients at risk for difficult intubation in the intensive care unit: development and validation of the MACOCHA score in a multicenter cohort study. Am J Respir Crit Care Med. 2013;187(8):832-9. [CrossRef] [PubMed]
22. Joshi R, Hypes CD, Greenberg J, Snyder L, Malo J, Bloom JW, et al. Difficult airway characteristics associated with first-attempt failure at intubation using video laryngoscopy in the intensive care unit. Ann Am Thorac Soc. 2017;14(3):368-75. [CrossRef] [PubMed]
23. Perbet S, De Jong A, Delmas J, Futier E, Pereira B, Jaber S, et al. Incidence of and risk factors for severe cardiovascular collapse after endotracheal intubation in the ICU: a multicenter observational study. Crit Care. 2015;19:257. [CrossRef] [PubMed]
24. Driver BE, Prekker ME, Moore JC, Schick AL, Reardon RF, Miner JR. Direct versus video laryngoscopy using the c-mac for tracheal intubation in the emergency department, a randomized controlled trial. Acad Emerg Med. 2016;23(4):433-9. [CrossRef] [PubMed]
25. Griesdale DE, Chau A, Isac G, Ayas N, Foster D, Irwin C, et al. Video-laryngoscopy versus direct laryngoscopy in critically ill patients: a pilot randomized trial. Can J Anaesth. 2012;59(11):1032-9. [CrossRef] [PubMed]
26. Janz DR, Semler MW, Lentz RJ, Matthews DT, Assad TR, Norman BC, et al. Randomized trial of video laryngoscopy for endotracheal intubation of critically ill adults. Crit Care Med. 2016;44(11):1980-7. [CrossRef] [PubMed]
27. Lascarrou JB, Boisrame-Helms J, Bailly A, Le Thuaut A, Kamel T, Mercier E, et al. Video laryngoscopy vs direct laryngoscopy on successful first-pass orotracheal intubation among ICU patients: A randomized clinical trial. JAMA. 2017;317(5):483-93. [CrossRef] [PubMed]

Cite as: Malo J, Hypes C, Natt B, Cristan E, Greenberg J, Morrissette K, Snyder L, Knepler J, Sakles J, Knox K, Mosier J. Airway registry and training curriculum improve intubation outcomes in the intensive care unit. Southwest J Pulm Crit Care. 2018;16(4):212-23. doi: https://doi.org/10.13175/swjpcc037-18 PDF 

April 2018 Critical Care Case of the Month

Clement U. Singarajah, MD

Phoenix VA Medical Center

Phoenix, AZ USA

History of Present Illness

A 70-year-old man was admitted for shortness of breath (SOB) secondary to a “COPD exacerbation/ILD”. A pulmonary consult was placed for possible interstitial lung disease (ILD). A thoracic CT scan for pulmonary embolism showed no embolism and no obvious ILD. He was treated for a COPD exacerbation with the usual therapy of antibiotics, steroids, nebulized bronchodilators and oxygen. He started to improve.

A few days later as he was preparing for discharge, the patient suddenly decompensated becoming more SOB (once more proving that this a dangerous time for patients in hospital). There were reports that this began after he choked and perhaps aspirated on some food and drink. His blood pressure remained stable, but he became tachycardic to 130 beats/min, hypoxic on 100% non-rebreathing mask with saturations of 92%. Obvious clinical acute respiratory failure was present. The patient was started on non-invasive ventilation but continued to deteriorate.  He was deemed too unstable to obtain a CT scan. EKG showed sinus tachycardia. The patient was transferred to the ICU for respiratory failure. A chest x-ray was obtained (Figure 1).

Figure 1. Panel A: Admission chest x-ray which was interpreted as not different from the patient’s previous chest x-ray. Panel B: Portable chest x-ray taken shortly after initiation of non-invasive ventilation just after arrival in the intensive care unit.

The portable chest x-ray taken in the ICU shows a new right-sided consolidation and which of the following? (Click on the correct answer to proceed to the second of six pages)

1. Left pleural effusion and a loculated pneumothorax with tension physiology
2. Left pneumothorax with tension physiology
3. Left pneumothorax without tension physiology
4. Left sided tension hydropneumothorax
5. None of the above

Cite as: Singarajah CU. April 2018 critical care case of the month. Southwest J Pulm Crit Care. 2018;16(4):183-91. doi: https://doi.org/10.13175/swjpcc042-18 PDF

Increased Incidence of Eosinophilia in Severe H1N1 Pneumonia during 2015 Influenza Season

Benjamin Deaton MD

Nicholas Villalobos MD

Andrea Mytinger DO

Michel Boivin MD

Department of Internal Medicine

University of New Mexico School of Medicine

Albuquerque, NM USA

Abstract

Background: A portion of patients with influenza develop a severe, life t-threatening illness requiring intensive care. We observed a significant number of critically ill influenza patients with eosinophilia during the 2015 influenza season in New Mexico.

Methods: Patients were identified sequentially by reviewing disposition records of all patients admitted to the University of New Mexico Hospital medical intensive care unit between October 2015 and May 2016 for a diagnosis of influenza.

Results: Eleven patients were identified who developed respiratory failure from influenza. Average age was 43.7 + 11.3 (SD) with an average SAPS-2 score of 52.0 + 13.9 (SD) on admission. All 11 were found to have H1N1 influenza. All 11 required mechanical ventilation vasopressor support. Ten patients survived. Notably, 6 (54.5%) developed peripheral eosinophilia (>300/μL) during their hospitalization and all but one of these did not have peripheral eosinophilia at the time of admission. Bronchoalveolar lavage was performed in 5 patients (45.5%) and none were consistent with eosinophilic pneumonia. Further data analysis revealed exploration revealed no significant differences in multiple parameters and no clear cut cause of drug-induced eosinophilia was identified.

Conclusion: During the 2015 influenza season in New Mexico, a disproportionate number of patients with H1N1 influenza and respiratory failure developed peripheral eosinophilia. Type 2 errors could have occurred due to low sample size. Given the unusual frequency of peripheral eosinophilia further studies regarding the association of influenza A and peripheral eosinophilia is warranted.

Introduction

Influenza pneumonia remains a cause of significant morbidity and mortality (1). The re-emergence of H1N1 influenza in 2009 was associated with particularly severe respiratory illness, acute respiratory distress syndrome (ARDS) and mortality (2). The ARDS associated with H1N1 influenza appeared to disproportionately affect younger individuals, compared to other strains of influenza A (2). During the 2015 influenza season H1N1 circulated relatively late in the southwestern United States (3). Intensivists caring for patients with severe H1N1 pneumonia at the University of New Mexico hospital noticed a series of cases associated with significant peripheral eosinophilia. Eosinophilia with influenza or its treatments has rarely been described (4). We therefore sought to examine all cases of severe influenza pneumonia during the 2015 influenza season for the prevalence of peripheral eosinophilia and to assess for potential associations.

Methods

This study was reviewed and approved by the Institutional Review Board of the University of New Mexico Health Sciences Center. Patients from the University of New Mexico Hospital (UNMH) adult Medical Intensive Care Unit (MICU) admitted between October 2015 through May 2016 were retrospectively screened for inclusion. Inclusion criteria included a diagnosis of influenza (using a PCR based assay of nasal swab), admission to the UNMH MICU and age ≥ 18 years. Exclusion criteria included patients admitted to the MICU where influenza did not lead to significant respiratory failure.

In this retrospective cohort chart review, data was collected for demographics, clinical parameters at presentation and throughout their hospital course, and interventions received. Patients were assessed for the presence of eosinophilia at any point during their hospital course. Eosinophilia was defined as a serum eosinophil count that exceeded the upper limit of normal on a complete blood count (0.3x10³ cells/microliter). Values are reported with their standard deviation. Statistical analysis was performed using Stata 14 for Mac. The data was explored using two-sided t-tests, Fisher’s exact and Chi-squared tests between the 2 groups with and without eosinophilia. The paper was partially presented in poster form at the 2017 American Thoracic Society International Congress in Washington, DC (5).

Results

Thirteen patients with influenza were identified. Two patients were excluded from further analysis as they did not meet the criteria of having respiratory failure, the remaining eleven were included in this study. The average age of patients in the study was 43.7 ±11.3 years with an average SAPS-2 score of 52.0 ± 13.9 on admission. All eleven patients in the study admitted with severe influenza A leading to respiratory failure during the 2015-2016 influenza season were found to be infected by the H1N1 strain of influenza. See Table 1 for further descriptors of the cohort.

Table 1. Baseline and treatment characteristics by group.

The peak eosinophil count of the group with normal eosinophil count was 0.1(+0.1) X10³ cells/µl compared to 1.9 (+ 2.1) X10³ cells/µl in the group with significant peripheral eosinophilia (p=0.06). The range of eosinophilia in the group with normal eosinophil count was 0.0-0.3 X10³ cells/µl, and 0.5-4.8 X10³ cells/µl in the group with eosinophilia. The group with normal eosinophil count reached a “peak” count after an average of 4.6 days, and the group with an elevated eosinophil count after 17.1 days (p<0.02).None of the patients who underwent bronchoscopy had a significant elevation in the bronchoalveolar lavage eosinophil count.

Discussion

During the 2015-2016 influenza season in New Mexico, critically ill patients at UNM hospital admitted with influenza pneumonia were infected with the H1N1 subtype. Over 50 percent of these patients developed peripheral eosinophilia at some point of their hospital course. Among those who underwent bronchoscopy, significant alveolar eosinophilia was not observed, suggesting against a pulmonary cause of eosinophilia, such as acute or chronic eosinophilic pneumonia. All patients were treated with oseltamivir, so an association with this treatment could not be determined. No demographic differences were noted between patients who vashad peripheral eosinophilia and those that did not. The patients with significant peripheral eosinophilia trended to have a longer ICU and hospital length of stay (LOS) but this did not reach statistical significance in this small cohort.

Type 2 errors (failure to detect a true difference between groups due to small numbers of subjects) could have occurred due to low sample size while exploring etiologies. Potential etiologies that could have explained the observed eosinophilia included drug effect, possibly due to oseltamivir, antibiotics, diuretics or other medications. A review of the literature reveals case reports of associations between eosinophilia and influenza vaccine (6,7). Acute eosinophilic pneumonia has also been associated with H1N1 infection, but eosinophilia was not demonstrated on broncho-alveolar lavage in our series (8.9). Potentially this could have been a reaction to epitopes of this particular strain of H1N1 influenza. However, there have yet to be reports of eosinophilia during the 2015-2016 influenza season in the literature. Perhaps local factors could have contributed to an increased incidence of significant peripheral eosinophilia. Anecdotally, the authors do not however recall an increased incidence of eosinophilia in patients admitted for diagnoses other than H1N1. Patients were screened for other causes of viral pneumonia, and there was no clear co-infection that was associated with influenza associated eosinophilia. It was also noted the time to peak eosinophil count was much later in the elevated eosinophil group, and in most it took 14 days for the count to peak. This suggests the stimulus for the eosinophilia was ongoing for considerable time during the admission.

In conclusion, we describe an unusually high incidence of peripheral eosinophilia in patients with severe H1N1 influenza during the 2015 flu season. This eosinophilia was not associated with alveolar eosinophilia. Further observation for the recurrence of this association of H1N1 influenza A and peripheral eosinophilia is warranted during future influenza seasons.

References

1. Rotrosen ET, Neuzil KM, Influenza: a global perspective. Pediatr Clin North Am. 2017;64:911-36. [CrossRef] [PubMed]
2. Davlin SL, Blanton L, Kniss K, et al. Influenza Activity - United States, 2015-16 Season and Composition of the 2016-17 Influenza Vaccine.MMWR Morb Mortal Wkly Rep. 2016 Jun 10;65(22):567-75. [CrossRef] [PubMed]
3. Uyeki TM. Influenza. Ann Intern Med. 2017 Sep 5;167(5):ITC33-ITC48. [CrossRef] [PubMed]
4. Deaton, BR., Mytinger, AK, Ahmed, S, et al. Peripheral eosinophilia associated with 2016 H1N1 influenza. Am J Resp Crit Care. 2017;195:A5787 [Abstract],
5. Hayashi R, Shimomura N, Hosojima M, et al. A case of non-episodic angioedema with eosinophilia induced by influenza vaccine. Eur J Dermatol. 2017;27:554-5. [CrossRef] [PubMed]
6. Solak B, Dikicier BS, Kara RO, Erdem T. DRESS syndrome potentially induced by allopurinol and triggered by influenza vaccine. BMJ Case Rep. 2016 Mar 30;2016. [CrossRef] [PubMed]
7. Larrañaga JM, Marcos PJ, Pombo F, Otero-González I. Acute eosinophilic pneumonia as a complication of influenza A (H1N1) pulmonary infection. Sarcoidosis Vasc Diffuse Lung Dis. 2016 Mar 29;33(1):95-7. [PubMed]
8. Jeon EJ, Kim KH, Min KH. Acute eosinophilic pneumonia associated with 2009 influenza A (H1N1). Thorax. 2010;65:268-70. [CrossRef] [PubMed]

Cite as: Deaton B, Villalobos N, Mytinger A, Boivin M. Increased incidence of eosinophilia in severe H1N1 pneumonia during 2015 influenza season. Southwest J Pulm Crit Care. 2018;16(3):146-9. doi: https://doi.org/10.13175/swjpcc021-18 PDF 

March 2018 Critical Care Case of the Month

Babitha Bijin MD

Jonathan Callaway MD

Janet Campion MD

University of Arizona

Department of Medicine

Tucson, AZ USA

Chief Complaints

• Shortness of breath
• Worsening bilateral LE edema

History of Present Illness

A 53-year-old man with history of multiple myeloma and congestive heart failure presented to the emergency department with complaints of worsening shortness of breath and bilateral lower extremity edema for last 24 hours. In the last week, he has had dyspnea at rest as well as a productive cough with yellow sputum. He describes generalized malaise, loss of appetite, possible fever and notes new bilateral pitting edema below his knees. Per patient, he had flu-like symptoms one week ago and was treated empirically with oseltamivir.

Past Medical History

• Multiple myeloma-IgG kappa with calvarial and humeral metastases, ongoing treatment with cyclophosphamide, bortezomib and dexamethasone
• Community acquired pneumonia 2016, treated with oral antibiotics
• Heart failure with echo 10/2017 showing moderate concentric left ventricular hypertrophy, left ventricular ejection fraction 63%, borderline left atrial and right atrial dilatation, diastolic dysfunction, right ventricular systolic pressure estimated 25 mm Hg
• Hyperlipidemia
• Chronic kidney disease, stage III

Home Medications: Aspirin 81mg daily, atorvastatin 80mg daily, furosemide 10mg daily, calcium / Vitamin D supplement daily, oxycodone 5mg PRN, chemotherapy as above

Allergies: No known drug allergies

Social History:

• Construction worker, not currently working due to recent myeloma diagnosis
• Smoked one pack per day since age 16, recently quit with 30 pack-year history
• Drinks beer socially on weekends
• Married with 3 children

Family History: Mother with hypertension, uncle with multiple myeloma, daughter with rheumatoid arthritis

Review of Systems: Negative except per HPI

Physical Exam

• Vitals: T 39.3º C, BP 80/52, P121, R16, SpO2 93% on 2L
• General: Alert man, mildly dyspneic with speech
• Mouth: Nonicteric, moist oral mucosa, no oral erythema or exudates
• Neck: No cervical neck LAD but JVP to angle of jaw at 45 degrees
• Lungs: Bibasilar crackles with right basilar rhonchi, no wheezing
• Heart: Regular S1 and S2, tachycardic, no appreciable murmur or right ventricular heave
• Abdomen: Soft, normal active bowel sounds, no tendernesses, no hepatosplenomegaly
• Ext: Pitting edema to knees bilaterally, no cyanosis or clubbing, normal muscle bulk
• Neurologic: No focal abnormalities on neurologic exam

Laboratory Evaluation

• Complete blood count: WBC 15.9 (92% neutrophils), Hgb/Hct 8.8/27.1, Platelets 227
• Electrolytes: Na⁺ 129, K⁺ 4.0, Cl^- 100, CO2 18, blood urea nitrogen 42, creatinine 1.99 (baseline Cr 1.55)
• Liver: AST 35, ALT 46, total bilirubin1.7, alkaline phosphatase 237, total protein 7.4, albumin 2.
• Others: troponin 0.64, brain naturetic peptide 4569, venous lactate 2.6

Chest X-ray

Figure 1. Admission chest x-ray.

Thoracic CT (2 views)

Figure 2. Representative images from the thoracic CT scan in lung windows.

What is most likely etiology of CXR and thoracic CT findings? (Click on the correct answer to proceed to the second of seven pages)

1. Coccidioidomycosis pneumonia
2. Pulmonary edema
3. Pulmonary embolism with infarcts
4. Staphylococcus aureus pneumonia
5. Streptococcus pneumoniae infection 

Cite as: Bijin B, Callaway J, Campion J. March 2018 critical care case of the month. Southwest J Pulm Crit Care. 2018;16(3):117-25. doi: https://doi.org/10.13175/swjpcc035-18 PDF 

Ultrasound for Critical Care Physicians: Ghost in the Machine

Ross Davidson, DO

Michel Boivin, MD 

Division of Pulmonary, Critical Care and Sleep Medicine

University of New Mexico School of Medicine

Albuquerque, NM USA

A 53-year-old woman presented to the emergency department after a sudden cardiac arrest at home. The patient had a history of asthma and tracheal stenosis and had progressive shortness of breath over the previous days. The patient’s family noticed a “thump” sound from the patient’s room, and found her apneic. They called 911 and began cardiopulmonary resuscitation. Paramedics arrived on the scene, found an initial rhythm of pulseless electrical activity. The patient eventually achieved return of spontaneous circulation and was transported to the hospital. On arrival the patient was in normal sinus rhythm, with a heart rate of 110 beats per minute. Blood pressure was 80/45 mmHg, on an epinephrine infusion. The patient was afebrile, endotracheally intubated, unresponsive and ventilated at 30 breaths per minute. An initial chest radiograph was compatible with aspiration pneumonitis and a small pneumothorax. Initial electrocardiogram on arrival had 1mm ST-segment depressions in leads V4 to V6. Transthoracic echocardiography was unsuccessful due to patient’s habitus and mechanical ventilation. Because of the patient’s hemodynamic instability and unknown cause of cardiac arrest, an urgent trans-esophageal echocardiogram (TEE) was performed (Videos 1-3).

Video 1. Mid-esophageal 4-chamber view of the heart.

Video 2. Upper esophageal long-axis view of the pulmonary artery and short axis view of the ascending aorta.

Video 3. Upper esophageal short axis view of the pulmonary artery with the ascending aorta in long axis. 

Based on the images presented what do you suspect is the etiology of the patient’s cardiac arrest? (Click on the correct answer for an explanation-no penalty for guessing, you can go back and try again)

1. Massive Pulmonary Embolism
2. Myocardial infarction
3. Pericardial Tamponade
4. Unable to determine

Cite as: Davidson R, Boivin M. Ultrasound for critical care physicians: ghost in the machine. Southwest J Pulm Crit Care. 2018;16(2):76-80. doi: https://doi.org/10.13175/swjpcc027-18 PDF 

February 2018 Critical Care Case of the Month

Robert A. Raschke, MD

University of Arizona College of Medicine-Phoenix

Phoenix, AZ

History of Present Illness

A 25-year-old was admitted to an outside hospital with an acute episode of nausea and vomiting and chronic progressive weakness.  He smoked 2 cigarettes per day and drank a 12-pack of beer per month.  He had a history of undefined chronic liver disease.

Physician Examination

Physical examination was reported as showing a chronically ill appearing man who was “weak” using crutches to ambulate.

The patient was made NPO and was rehydrated with intravenous normal saline.

Which of the following are indicated at this time? (Click on the correct answer to proceed to the second of four pages)

1. Creatinine phosphokinase (CPK)
2. Serum potassium
3. Thyroid studies
4. 1 and 3
5. All of the above

Cite as: Raschke RA. February 2018 critical care case of the month. Southwest J Pulm Crit Care. 2018;16(2):62-6. doi: https://doi.org/10.13175/swjpcc009-18 PDF

January 2018 Critical Care Case of the Month

Theodore Loftsgard, APRN, ACNP 

Department of Anesthesiology and Critical Care

Mayo Clinic Minnesota

Rochester, MN USA

History of Present Illness

The patient is a 51-year-old woman admitted with a long history of progressive shortness of breath.  She has a long history of “heart problems”. She uses supplemental oxygen at 1 LPM by nasal cannula.

Past Medical History, Social History and Family History

She also has several comorbidities including renal failure with two renal transplants and a history of relatively recent RSV and CMV pneumonia. She is a life-long nonsmoker. Her family history is noncontributory.

Physical Examination

• Vital signs: Blood pressure 145/80 mm Hg, heart rate 59 beats/min, respiratory rate 18, T 37.0º C, SpO2 91% of 1 LPM.
• Lungs: Clear.
• Heart: Regular rhythm with G 3/6 systolic ejection murmur at the base.
• Abdomen: unremarkable.
• Extremities: no edema

Which of the following should be performed? (Click on the correct answer to proceed to the second of seven pages)

1. Brain naturetic peptide (BNP)
2. Chest x-ray
3. Echocardiogram
4. Electrocardiogram
5. All of the above

Cite as: Loftsgard T. January 2018 critical care case of the month. Southwest J Pulm Crit Care. 2018;16(1):1-7. doi: https://doi.org/10.13175/swjpcc155-17 PDF

December 2017 Critical Care Case of the Month

Michael B. Gotway, MD

Department of Radiology

Mayo Clinic Arizona

Scottsdale AZ USA

Clinical History: A 57-year-old man with no known previous medical history was brought to the emergency room via ambulance and admitted to the intensive care unit with a compliant of severe chest pain in the substernal region and epigastrium. The patient was awake and alert and did not complain of shortness of breath.

Physical examination was largely unremarkable and the patient’s oxygen saturation was 98% on room air. The patient’s vital signs revealed tachycardia (105 bpm) and his blood pressure was 108 mmHg / 60 mmHg.

Laboratory evaluation showed a slightly elevated white blood cell count (13 x 10⁹ cells/L), but his hemoglobin and hematocrit values were with within normal limits, as was his platelet count. 

Which of the following diagnoses are appropriate considerations for this patient’s condition? (Click on the correct answer to proceed to the second of nine pages)

1. Acute pericarditis
2. Aortic dissection
3. Community-acquired pneumonia
4. Myocardial infarction
5. All of the above

Cite as: Gotway MB. December 2017 critical care case of the month. Southwest J Pulm Crit Care. 2017;15(6):241-52. doi: https://doi.org/10.13175/swjpcc145-17 PDF 

November 2017 Critical Care Case of the Month

Stephanie Fountain, MD

Pulmonary and Critical Care Medicine

Banner University Medical Center Phoenix

Phoenix, AZ USA

History of Present Illness

A 56-year-old man presented with “food stuck in throat” since eating steak 18 hours prior to presentation. He is unable to eat or drink and has a sore throat. He is able to speak but has a “hoarse voice.” He denied drooling.

Past Medical History, Family History, and Social History

• He described himself as “healthy” and had not sought medical care in years.
• Former smoker but quit 2 years ago.
• He uses alcohol daily.
• He denied illicit drug use.

Physical Exam

• Afebrile, blood pressure 137/74 mm HG, heart rate 74 beats/min, SpO2 98% on room air.
• Physical exam was normal

Which of the following should be done next? (Click on the correct answer to proceed to the second of six pages)

1. Esophagogastroduodenoscopy (EGD)
2. Papain (Adolph’s Meat Tenderizer®) administration
3. Tracheostomy
4. 1 and 3
5. All of the above

Cite as: Fountain S. November 2017 critical care case of the month. Southwest J Pulm Crit Care. 2017;15(5):191-8. doi: https://doi.org/10.13175/swjpcc130-17 PDF

A New Interventional Bronchoscopy Technique for the Treatment of Bronchopleural Fistula

Evan Denis Schmitz, MD

Abstract

A patient receiving mechanical ventilation with multiple left hydropneumothoraces had a persistent air leak through the thoracostomy tube. The leak was temporarily resolved by interventional bronchoscopy at the bedside in the ICU. Because of the limited resources available at the hospital, a Swan-Ganz catheter was inserted into the left upper lobe bronchus, inflated and left in place. The air leak ceased and the left upper lobe bronchus was occluded with an autologous blood plug by infusing the patient’s own blood through the distal port of the catheter. The patient’s oxygenation improved significantly. The effects persisted for 2.5 hours until the air leak returned while the patient remained intubated. Such a technique may be useful when managing persistent air leaks.

Introduction

An air leak during mechanical ventilation despite the insertion of a thoracostomy tube can be detected by the bubbling of air through the air seal in the chest drainage system (1). A persistent air leak (PAL) is often defined as persistence of the air leak beyond 24 hours, which can hinder ventilation and inhibit lung expansion. Furthermore, the leak may inhibit healing of the fistula between the lung and the pleural space. Recommendations for the management of PALs include surgical repair as the gold standard for treatment (1,2). However, published anecdotal reports describe successful treatment of PALs with endobronchial insertion of fibrin sealants, ethanol injection, metal coils, Watanabe spigots and endobronchial valves. Success is also reported with chemical and autologous blood patch pleurodesis (1). We report a bedside interventional bronchoscopy technique using a Swan-Ganz catheter for the treatment of PALs while intubated and ventilated. A Swan-Ganz catheter is inserted into a lobar bronchus using direct visualization with a bronchoscope, the balloon is inflated and left in place while an autologous blood plug is created utilizing the distal port of the catheter.

Case Presentation

A 69-year-old man with no prior medical contact presented to the emergency department with severe shortness of breath and altered mental status. He was intubated in the emergency department for hypoxia. On arrival to the ICU he was in hypoxic respiratory failure and septic shock with a PaO₂ in the 40s. His ventilator plateau pressures were 40-50 cm H₂O. Chest radiography revealed moderate pneumomediastinum and multiple loculated hydropneumothoraces involving the left lung with suspected necrotic left upper lobe (Figure 1).

Figure 1. Portable AP chest x-ray showing left lung loculated hydropneumothoraces in the apex, medial and lateral walls of the left chest, subcutaneous emphysema, mediastinal emphysema and very low lung volumes. There are right apical and lower lobe areas of consolidation. A left thoracostomy tube is in place.

A 32 Fr thoracostomy tube was placed in the left intercostal space lateral to the nipple in the mid-axillary. The larger thoracostomy tube was chosen because of concern that the smaller pig-tailed catheters might not be adequate to control the leak. Plateau pressure improved to 30 cm H2O.

Despite a low tidal volume ventilator strategy and -40 cm H₂O suction through the thoracostomy tube, the patient had an air leak through the thoracostomy tube which continued to bubble in the water seal chamber during both inspiration and expiration. The air leak did not improve over the ensuing 24 hours and subcutaneous emphysema worsened when attempts were made to decrease suction which was confirmed by physical exam and chest x-ray. Selective right lung ventilation led to inadequate ventilation as evidenced by increasing end-tidal CO_2.

To determine and attempt to control the source of the persistent air leak, an interventional bronchoscopy was performed at bedside. Because other devices to such as metal coils, endobronchial valves, fibrin glue and a YAG laser were unavailable, a 6 Fr Swan-Ganz catheter was used. The Swan-Ganz catheter was threaded through the opening of the bronchoscope adaptor down the endotracheal tube to 3 cm above the carina. A flexible bronchoscope was then advanced along the side of the catheter through the bronchoscope adaptor and down the endotracheal tube. The catheter was not inside the working channel of the bronchoscope. The catheter was manipulated along with the bronchoscope, taking advantage of the inherent bend in the catheter, into the left mainstem bronchus and into the left upper lobe bronchus just distal to the lingular bronchus and inflated (Figure 2).

Figure 2. Panel A: Bronchoscopic view showing the Swan-Ganz catheter in the left upper lobe bronchus. Panel B: Chest x-ray confirming the Swan-Ganz catheter in the left upper lobe with the balloon inflated (arrow).

The massive air leak stopped completely. A blood plug was then created by instilling 20 ml of the patient’s own blood into the distal port of the catheter distal to the balloon along with 5 ml of 1:1000 epinephrine. The bronchoscope was used to hold the balloon in place for 10 minutes while the blood clotted. The bronchoscope was carefully removed and the catheter with the balloon inflated was left in place (Figure 3).

Figure 3. Bronchoscopic view showing the catheter passing into the left upper lobe bronchus with the surrounding blood plug.

The bronchoscope adaptor was taped post-bronchoscopy at the opening with an occlusive dressing so no air could leak around the catheter. The patient tolerated the procedure well. The air leak was successfully stopped with no evidence of worsening pneumothoraces. After PaO₂ increased from the 40s on admission to the 170s after the PAL was stopped. Chest x-ray at 1 and 3 hours showed no evidence of worsening pneumothorax with the Swan-Ganz catheter still in place and inflated in the left upper lobe bronchus. After 2.5 hours, a smaller air leak did return but was present only during inspiration.

Discussion

A PAL during mechanical ventilation can be a serious complication of ventilator therapy. It can lead to poor lung expansion, ventilation/perfusion mismatch, direct extension of airway infection into the pleural space, and an inability to maintain positive end-expiratory pressure. Patients with a PAL have increased complications, including ICU readmission, pneumonia, and a longer hospital stay (3,4). Fortunately, it appears to be relatively rare. In a retrospective study only 39 out of 1,700 mechanically ventilated patients had a PAL defined as lasting for greater than 24 hours (5).

The American College of Chest Physicians guidelines published in 2001 and the 2010 British Thoracic Society guidelines on pleural disease recommend waiting for about 4 days and then seeking surgical evaluation for a PAL (2,6). It was recommended that consideration should be given to placing the thoracostomy tube to water seal rather than to suction. However, this may not be possible in patients with a large persistent air leak that complicates ventilation. In those instances, a variety of endobronchial and pleural interventions have been attempted. Although the reports are anecdotal, most achieved success with either none or minimal complications (1). There have been two basic approaches to treat PALs; sealing the air leak from the bronchial side or from the pleural side. Those therapies administered through the bronchoscope include fibrin sealant, metal coils, Watanabe spigots, synthetic hydrogel, platelet gel, endobronchial valves and YAG laser (1). Complications were infrequent and minor. Ethanolamine and ethanol have also been used but there appear to be more complications with those treatments. From the pleural side, blood patch and chemical pleurodesis have been used successfully (1). However, chemical pleurodesis might result in a trapped lung.

The technique reported here can be performed with materials available in the ICU. A torqueable guidewire can be inserted if needed to help increase the catheter stiffness and help with advancement of the catheter into the individual bronchus to identify the source of the bronchopleural fistula. Alternatives to a blood patch might include occlusion of the culprit bronchus with the patient’s own mucus and argon plasma coagulation to form a clot. A blood patch can be used to determine the potential success of a more permanent material to occlude the bronchus, such as a fibrin seal, synthetic hydrogel, laser, or before attempting endobronchial valve placement.

Conclusion

Bedside endobronchial management of PAL is feasible using a flexible bronchoscope and Swan-Ganz catheter for localization, tamponade and delivery of a blood plug.

References

1. Dugan KC, Laxmanan B, Murgu S, Hogarth DK. Management of persistent air leaks. Chest. 2017;152(2):417-23. [CrossRef] [PubMed]
2. Baumann MH, Strange C, Heffner JE. Management of spontaneous pneumothorax: an American College of Chest Physicians Delphi consensus statement. Chest. 2001;119(2):590-602. [CrossRef] [PubMed]
3. Liberman M, Muzikansky A, Wright CD, et al. Incidence and risk factors of persistent air leak after major pulmonary resection and use of chemical pleurodesis. Ann Thorac Surg. 2010;89(3):891-897. [CrossRef] [PubMed]
4. DeCamp MM, Blackstone EH, Naunheim KS, et al. Patient and surgical factors influencing air leak after lung volume reduction surgery: lessons learned from the National Emphysema Treatment Trial. Ann Thorac Surg. 2006;82(1):197-206. [CrossRef] [PubMed]
5. Pierson DJ, Horton CA, Bates PW. Persistent bronchopleural air leak during mechanical ventilation. A review of 39 cases. Chest. 1986;90(3):321-3. [CrossRef] [PubMed]
6. Havelock T, Teoh R, Laws D, et al. Pleural procedures and thoracic ultrasound: British Thoracic Society Pleural Disease Guideline 2010. Thorax. 2010;65(suppl 2):ii61-ii76. [CrossRef] [PubMed]

Cite as: Schmitz ED. A new interventional bronchoscopy technique for the treatment of bronchopleural fistula. Southwest J Pulm Crit Care. 2017;15(4):174-8. doi: https://doi.org/10.13175/swjpcc120-17 PDF