Left Ventricular Assist Devices: A Brief Overview

Bhargavi Gali MD

Department of Anesthesiology and Perioperative Medicine

Division of Critical Care Medicine

Mayo Clinic Minnesota

Rochester, MN, USA

Introduction

Second and third generation left ventricular assist devices (LVAD) have been increasingly utilized as both a bridge to transplantation and as destination therapy (in patients who are not considered transplant candidates) for advanced heart failure. Currently approximately 2500 LVADs are implanted yearly, with an estimated one year survival of >80% (1). Almost half of these patients undergo implantation as destination therapy. A recent systematic review and meta-analysis found no difference in one-year mortality between patients undergoing heart transplantation in comparison with patients undergoing LVAD placement (2).

Early LVADs were pulsatile pumps, but had multiple limitations including duration of device function, and requirement for a large external lead that increased risk of infection. Currently utilized second and third generation devices are continuous flow (first generation were pulsatile flow). Second generation devices have axial pumps (HeartMate II®). The third generation LVADs ((HeartMate III®), HVAD®) are also continuous flow, with centrifugal pumps, which are thought to decrease possibility of thrombus formation and increase pump duration in comparison to the second generation axial pumps. It is also felt that a lack of mechanical bearings contributes to this effect.

LVADs support circulation by either replacing or supplementing cardiac output. Blood is drained from the left ventricle with inflow cannula in the left ventricular apex to the pump, and blood is returned to the ascending aorta via the outflow cannula (3) (Figure 1).

Figure 1. Third generation Left Ventricular Assist Device. Heartware System ™. Continuous flow left ventricular assist device (LVAD) configuration. One of the third generation LVADs is the HeartWare System. With this device the inflow cannula is integrated into the pump. The pump is attached to the heart in the pericardial space, with the outflow cannula in the aorta. A driveline connects the device to the control unit. This control unit is attached to the two batteries. (Figure used with permission from Medtronic).

The device assists the left ventricle by the action of the axial (second generation) or centrifugal (third generation) pump that rotates at a very high speed and ejects the blood into the aorta via the outflow cannula. A tunneled driveline connects the pump to the external controller that operates the pump function. The controller connects to the power source via two cables, which can be battery or module-powered.

LVADs offload volume from the left ventricle, and decrease left ventricular work. Pulmonary pressures and the trans pulmonary gradients are also decreased by the reduced volume in the left ventricle (4). End organ perfusion is improved secondary to enhanced arterial blood pressure and micro perfusion.

There are four main parameters of pump function:

• Pump speed: the speed at which the LVAD rotors spin, and is programmed. Measured in RPM.
• Pump power: the wattage needed to maintain speed and flow, which is the energy needed to run the pump. Measured in Watts.
• Pump flow: estimate of the cardiac output, which is the blood returned to the ascending aorta, and is based on pump speed and power. Measure in L/min
• Pulsatility index (PI): a calculated value that indicates assistance the pump provides, in relation to intrinsic left ventricular A higher number indicates higher left ventricular contribution to pulsatile flow.

The cardiac output of currently utilized LVADs is directly related to pump speed and inversely related to the pressure gradient across the pump. As the pump speed is fixed, right ventricular failure can decrease the volume of blood transmitted to the pump and decrease LVAD flow (3, 4). With right ventricular failure, inotropic support may be needed to improve the LVAD pump flow. High afterload, such as may be seen with an increase in systemic vascular resistance can decrease pump flow.

Complications

Adverse events occur in more than 70% of LVAD patients in the first year (5). These complications include infections, bleeding, stroke, and LVAD thrombosis. More than 50% of patients are readmitted within the first 6 months after LVAD implantation (6).

Driveline infections are the most commonly reported LVAD infection, and are the most likely to respond to treatment (7). Pump pocket infections may require debridement plus/minus antibiotic bead placement. Bloodstream infections are less commonly reported, and more difficult to treat, and many patients are placed on chronic suppressive antibiotic therapy (7). There is a possible association between stroke and bloodstream infection, reported in some studies. Patients who were younger and had a higher body mass index were noted to have a higher incidence of LVAD infections.

Gastrointestinal bleeding is a major cause of nonsurgical bleeding, reported in almost 30% of patients after LVAD placement (1). Patients may develop acquired von Willebrand factor deficiency secondary to high shear forces in the LVAD that lead to breakdown of von Willebrand protein (6). Antithrombotic therapy is commonly instituted after LVAD implantation which also increases risk of bleeding. A high incidence of arteriovenous malformations is reported in these patients, although the etiology is not clear. Transfusion, holding antithrombotic therapy, and identifying possible sources are included in the standard approach to management.

There is a high risk of both ischemic and hemorrhagic strokes in the first year after LVAD placement (8). Surgical closure of the aortic valve and off-axis positioning of the cannulas have been suggested as altering shear forces, increasing thrombotic risk, and thus risk of stroke.  Post-surgical risks may include pump thrombosis, infections, supratherapeutic INR, and poorly controlled hypertension. Early diagnosis has led to consideration of interventions such as thrombectomy (8).

LVAD thrombosis can occur on either cannula (inflow or outflow) or the pump. Typically patients receive ongoing anticoagulation, commonly with warfarin, and antiplatelet agents, and often aspirin. Heartmate II® may have higher rate of thrombosis than HVAD or Heart Mate 3, although this is under debate (6). Thrombotic complications range in severity from asymptomatic increase in lactate dehydrogenase or plasma-free hemoglobin, to triggering of LVAD alarms, up to development of heart failure. The inflow and outflow cannulas and pump can be the site of thrombosis. Management typically involves revising the antithrombotic management. If there is no improvement or worsening, replacement of LVAD may be indicated. There is limited evidence to suggest that systemic thrombolysis may be of benefit in treating pump thrombosis, particularly in regards to the HVAD, though better data would be useful

Procedural Management

When a patient with an LVAD requires non cardiac surgery, optimal management includes having an on-site VAD technician, and close involvement of VAD cardiology and cardiac surgery in consultation. Anticoagulation will often be transitioned to heparin infusion prior to elective procedures (9). Suction events (LV wall is sucked into the inflow cannula) can occur secondary to under filled left heart, and this can become more apparent perioperatively. This can also decrease right heart contractility by moving the interventricular septum to the left, and thus decrease cardiac output. Management often involves fluid bolus. Suction events can lead to decreased flow, left ventricular damage, and ventricular arrhythmias. Hemodynamic management can be challenging with non-pulsatile flow, and placement of an arterial line can facilitate optimal management. Postoperative care in a monitored setting is beneficial in case of further volume related events and to watch for bleeding.

Emergent Complications

Arrhythmias occur in many patients after LVAD implantation. Atrial arrhythmias are reported in up to half of LVAD patients, and ventricular arrhythmias in 22-59% (10, 11).  Loss of AV synchrony can lead to decreased LV filling and subsequent RV failure. Rhythm or rate control with rapid atrial arrhythmias is necessary to decrease development of heart failure. Ventricular arrhythmias may be hemodynamically tolerated for some time secondary to the LVAD support (6).  If there is concern that the inflow cannula is touching the LV septum, as may occur with severe hypovolemia, echocardiography can help determine if volume resuscitation should be the initial step in treating ventricular arrhythmia.

If cardiac arrest occurs, the first step of cardiopulmonary resuscitation in patients with LVAD is assessment of appropriate perfusion via physical examination (12). If perfusion is poor or absent, assessment of LVAD function should take place. If the LVAD is not functioning appropriately, checking for connections and power is the next step. If unable to confirm function or restart LVAD, chest compressions are indicated by most recent guidelines from the American Heart Association. There is always concern of dislodgement of LVAD cannula or bleeding during these situations.

Conclusion

Currently implanted LVADS are continuous flow, and provide support via a parallel path from the left ventricle to the aorta. As the number of patients with LVADs increase all medical providers should have a basic understanding of the function and common complications associated with these devices. This will enhance the ability to initiate appropriate care.

References

1. Kirklin JK, Pagani FD, Kormos RL, et al. Eighth annual INTERMACS report: Special focus on framing the impact of adverse events. J Heart Lung Transplant. 2017 Oct;36(10):1080-6. [CrossRef] [PubMed]
2. Theochari CA, Michalopoulos G, Oikonomou EK, et al. Heart transplantation versus left ventricular assist devices as destination therapy or bridge to transplantation for 1-year mortality: a systematic review and meta-analysis. Annals of Cardiothoracic Surgery. 2017;7(1):3-11. [CrossRef] [PubMed]
3. Lim HS, Howell N, Ranasinghe A. The physiology of continuous-flow left ventricular assist devices. J Card Fail. 2017;23(2):169-80. [CrossRef] [PubMed]
4. Roberts SM, Hovord DG, Kodavatiganti R, Sathishkumar S. Ventricular assist devices and non-cardiac surgery. BMC Anesthesiology. 2015;15(1):185. [CrossRef] [PubMed]
5. Miller LW, Rogers JG. Evolution of left ventricular assist device therapy for advanced heart failure: a review. JAMA Cardiol. 2018 Jul 1;3(7):650-8. [CrossRef] [PubMed]
6. DeVore AD, Patel PA, Patel CB. Medical management of patients with a left ventricular assist device for the non-left ventricular assist device specialist. JACC Heart Fail. 2017 Sep;5(9):621-31. [CrossRef] [PubMed]
7. O'Horo JC, Abu Saleh OM, Stulak JM, Wilhelm MP, Baddour LM, Rizwan Sohail M. Left ventricular assist device infections: a systematic review. ASAIO J. 2018 May/Jun;64(3):287-294. [CrossRef] [PubMed]
8. Goodwin K, Kluis A, Alexy T, John R, Voeller R. Neurological complications associated with left ventricular assist device therapy. pert Rev Cardiovasc Ther. 2018 Dec;16(12):909-17. [CrossRef] [PubMed]
9. Barbara DW, Wetzel DR, Pulido JN, et al. The perioperative management of patients with left ventricular assist devices undergoing noncardiac surgery. Mayo Clinic Proceedings. 2013;88(7):674-82. [CrossRef] [PubMed]
10. Enriquez AD, Calenda B, Gandhi PU, Nair AP, Anyanwu AC, Pinney SP. Clinical impact of atrial fibrillation in patients with the heartmate ii left ventricular assist device. J Am Coll Cardiol. 2014 Nov 4;64(18):1883-90. [CrossRef] [PubMed]
11. Nakahara S, Chien C, Gelow J, et al. Ventricular arrhythmias after left ventricular assist device. Circ Arrhythm Electrophysiol. 2013 Jun;6(3):648-54. [CrossRef] [PubMed]
12. Peberdy MA, Gluck JA, Ornato JP, et al. Cardiopulmonary resuscitation in adults and children with mechanical circulatory support: a scientific statement from the American Heart Association. Circulation. 2017;135(24):e1115-e34.`[CrossRef] [PubMed]

Cite as: Gali B. Left ventricular assist devices: a brief overview. Southwest J Pulm Crit Care. 2019;19(2):68-72. doi: https://doi.org/10.13175/swjpcc039-19 PDF 

Design of an Electronic Medical Record (EMR)-Based Clinical Decision Support System to Alert Clinicians to the Onset of Severe Sepsis

Stephanie Fountain, MD

James Perry III, MD

Brenda Stoffer

Robert Raschke, MD

Banner University Medical Center Phoenix

Phoenix, AZ, USA

Abstract

Background: The aim of our study was to design an electronic medical record ­based alert system to detect the onset of severe sepsis with sensitivity and positive predictive value (PPV) above 50%.

Methods: The PPV for each of seven potential criteria for suspected infection (white blood cell count (WBCC) >12 or <4 x 10⁹ /L, immature granulocyte count >0.1 K/uL or immature granulocyte % >1%, temperature >38 C. or <36 C. or the initiation of broad­spectrum antibiotics) was determined by chart review of 160 consecutive patients who had evidence of organ system failure (as defined by standard criteria)plus at least one of the proposed criteria. Then, using only criteria with calculated PPV >50%, the charts of sixty consecutive patients who met CMS criteria for severe sepsis were reviewed to calculate the sensitivity of organ dysfunction plus any one of the suspected infection criteria.

Results: Four proposed criteria for suspected infection had PPV >50%: WBCC >12 x 10 9 /L (69%; 95%CI:53­84%), Temperature >38C. (84%; 95%CI:68­100%), Temperature <36C. (57% 95%CI:36­78%), and initiation of antibiotics (70% 95%CI:56­84%). These four criteria were present in 53/60 of the patients with severe sepsis by CMS criteria, yielding a sensitivity of 88.3% (95%CI: 80.2­96.4%). Alert criteria were satisfied before the onset of severe sepsis in 25/53 cases, and within 90 minutes afterwards in 28/53 cases.

Conclusions: Our criteria for suspected infection plus organ dysfunction yields reasonable sensitivity and PPV for the detection of severe sepsis in real­time.

Editor's Note: For accompanying editorial click here

Introduction

The American College of Chest Physicians and the Society for Critical Care Medicine define sepsis as a systemic inflammatory syndrome in response to infection and defined sepsis as “severe” when associated with acute organ dysfunction (1,2). The incidence of severe sepsis varies depending on the method of data abstraction from 300 to >1,000 per 100,000 person-years with an in-hospital mortality of 14.7% to 29.9% (3). Severe sepsis was estimated to cost U.S. healthcare system more than $24 billion in 2007 (4). The incidence and mortality of severe sepsis is expected to continue to rise (3-6).

Early recognition of severe sepsis and rapid implementation of standardized treatment bundles is associated with improved patient outcomes (7-12), but compliance rates with standardized time-sensitive treatment bundles for severe sepsis are generally in the 30% range (13). One reason may be that clinicians do not always recognize the onset of severe sepsis and therefore don’t have the opportunity to initiate all the elements required for bundle compliance in time. Therefore, a system that could alert providers to the onset of severe sepsis could help them achieve bundle compliance.

Clinical Decision Support Systems (CDSSs) use innovative software incorporated into electronic medical records (EMRs) to augment the awareness and expert knowledge of clinicians by providing pertinent and timely information at the point of care. CDSSs are adept at performing surveillance of electronic data to identify patients with vital signs and laboratory findings consistent with clinical deterioration. Several researchers have previously attempted to identify patients with severe sepsis in real-time with EMR-based CDSSs, but these systems suffered poor positive predictive value (PPV) and uncertain sensitivity (14,15). The PPV of a CDSS surveillance alert is important because it is inversely related to the proportion of false alerts. False alerts lead to clinician alert fatigue and subsequent disregard of alert recommendations (16,17).  High sensitivity is another important operating characteristic, but sensitivity is typically only achievable at the cost of reducing PPV. 

The goal of this pilot study was to develop criteria that could be used in a CDSS to identify patients at the onset of severe sepsis in real-time in order to alert clinicians. We chose to operationalize severe sepsis as organ system dysfunction due to infection, without requiring systemic inflammatory response syndrome, since a recent study that showed that the requirement of SIRS in the definition of severe sepsis excludes 1-in-8 patients suffering organ system dysfunction due to infection (18).  Organ dysfunction already has a standard definition based on laboratory results and vital signs (2) that are  discrete and easily extracted from the EMR by CDSS logic, but suspected infection does not.   Thus, a specific aim of this study is to determine optimal EMR-based criteria to define suspected infection in relation to the diagnosis of severe sepsis.  Our hypothesis was that we could identify a set of criteria for suspected infection which would have acceptable sensitivity and PPV for severe sepsis when combined with standard organ system dysfunction criteria.      

Methods

We chose seven potential criteria to identify suspected infection: the presence of a white blood cell count (WBCC) >12 x 10⁹/L or <4 x 10⁹/L, immature granulocyte count >0.1 K/uL or immature granulocyte % >1%, temperature >38 C. or <36 C. or the initiation of broad-spectrum antibiotics (piperacillin/tazobactam, third or fourth-generation cephalosporin, aminoglycoside, carbapenem, or vancomycin).  Organ system dysfunction was identified in the EMR as previously described and delineated in table 1.  

Table 1. Suspected infection and organ dysfunction criteria.

Our study occurred in two phases.  In the first, we tested individual criteria related to suspected infection in order to determine which had PPV >50% and were therefore incorporated into the second phase of the study.  In the second phase, we combined those accepted criteria for suspected infection with organ system dysfunction criteria and calculated the sensitivity for the diagnosis of severe sepsis as defined by Centers for Medicare and Medicaid (CMS).

Phase 1.  We used Cerner Discern^® to access clinical data in our Cerner Millennium^® EMR (Cerner Corporation, North Kansas City MO, USA) in order to identify a retrospective cohort of 160  Banner Health inpatients who satisfied any one of the seven potential suspected infection criteria plus one organ system dysfunction criteria (Table 1) within an eight-hour window.

The cohort consisted of four groups of forty patients each based on the type of suspected infection criteria present: abnormal WBCC, abnormal temperature, elevated immature granulocytes and initiation of antibiotics.  Patients were also selected so that half met criteria in the emergency department and half on the hospital wards.  Patient selection was otherwise consecutive. Chart reviews were performed by physician research staff to determine whether each patient was suffering the onset of severe sepsis at the time suspected infection and organ dysfunction criteria were satisfied. Such patients were considered to be true positive for the purposes of calculating PPVs. We decided a-priori that individual criteria that did not achieve at least 50% PPV would not be used in our final list of accepted criteria for suspected infection to be used in phase 2 of our study. We also compared PPV for each criteria between emergency department patients and inpatients.

Phase 2. The charts of sixty consecutive patients who met CMS criteria for severe sepsis in Banner Health were reviewed to calculate sensitivity of the combination of any one of the suspected infection criteria accepted in phase 1, plus one organ system dysfunction criteria occurring together within a six-hour window. The gold standard for the diagnosis of severe sepsis, and the time of onset of severe sepsis, were determined using CMS criteria by trained Banner Health data extraction staff for the primary purpose of regulatory reporting to CMS. The chart of each patient identified with severe sepsis by CMS methodology was reviewed to determine how many exhibited criteria for suspected infection and organ system dysfunction within 8 hours before, or 90 minutes after the onset of severe sepsis determined by CMS methodology.  [The rationale for this time window was that a hypothetical alert triggered by these criteria would only be valuable if it identified patients before, or shortly after the onset of severe sepsis].  We considered these to be true positive for the purposes of calculating sensitivity.

Results

Phase 1: PPVs with 95% confidence intervals for each of the potential criteria for suspected infection are listed in Table 2 below.

Table 2. PPV and 95% CI for individual suspected infection criteria (when found in temporal association with organ system dysfunction) for the clinical diagnosis of severe sepsis.

Only WBCC had a significantly different PPV when used in the emergency department vs the inpatient wards:  84% vs 50% (p=0.03).   

Immature granulocytes and WBCC <4 x 10⁹/L had PPV <50% and could be excluded from the set of accepted criteria with no loss of sensitivity. The set of accepted criteria include: WBCC >12 x 10⁹/L. temperature >38 or <36 and initiation of antibiotics. Finding any one of these accepted criteria in association with organ system dysfunction yielded a PPV of 70% (95%CI: 61-78%) for the diagnosis of severe sepsis.  

In 35/115 cases in which patients with one of these accepted criteria for suspected infection were not suffering an infection (false positive) the actual diagnoses included: cardiovascular diseases (s/p coronary artery bypass, myocardial infarction, cardiogenic shock), post-operative state, endocrinological disorders (hypothyroidism, diabetic ketoacidosis, adrenal failure), central nervous system pathology (intracranial hemorrhage, subarachnoid hemorrhage, seizure), obstetrical complications (placenta previa, spontaneous hemorrhage), and gastrointestinal hemorrhage.

Conclusions

Our data suggests that the best criteria set for suspected infection are likely to be: WBCC >12 x 10⁹/L, temperature >38 or <36 C. or initiation of broad spectrum antibiotics. The PPV of this set of criteria is likely to be >60%.  Leukopenia, and elevated immature granulocyte counts each had poor PPV and their exclusion would not significantly diminish the sensitivity of the set of criteria. 

Compared to other alert systems, this logic is novel for its abandonment of the use of SIRS criteria and the inclusion of antibiotic initiation. It could be argued that initiation of antibiotics should not be used to identify suspected infection because the clinician starting antibiotics is obviously already aware of infection.  However, unpublished analysis of 323 Banner health patients who qualified for severe sepsis by CMS criteria showed that 76% of those who failed bundle compliance received appropriate and timely antibiotics, but failed other important aspects of care, such as getting blood cultures before starting antibiotics and assessing lactate concentration. This suggests that a severe sepsis alert, triggering when a clinician enters an order for antibiotics could potentially assist the clinician in ordering other bundle elements. Exclusion of antibiotic initiation from our accepted criteria would have reduced the sensitivity of our alert logic to 75%.

The operating characteristics of our CDSS compares favorably to four previously published severe sepsis surveillance CDSSs which utilized SIRS criteria (see table 3 below). 

Table 3. Operating characteristics of CDSSs designed to provide surveillance for severe sepsis.

One of the strengths of this alert logic is that is it widely generalizable. It only includes data that is collected on most, if not all, hospitalized patients. It does not require additional tests or measurements that may limit its utility to a smaller patient population. It does not require physicians or ancillary staff to perform additional tasks or deviate from their standard workflow. Another strength of this logic is that it was created within the software program Cerner Discern^® in our Cerner Millennium^® EMR, one of the most widely used EMRs across the country. This would potentially allow seamless integration into any hospital system using this software, improving patient care and fulfilling “meaningful use” mandate of the Affordable Care Act.  However, our study is only a small pilot study. These results will need further validation using a larger data set. Further studies are needed to show whether a CDSS using these criteria can improve clinical outcomes of patients with severe sepsis.

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Cite as: Fountain S, Perry J III, Stoffer B, Raschke R. Design of an electronic medical record (EMR)-based clinical decision support system to alert clinicians to the onset of severe sepsis. Southwest J Pulm Crit Care. 2016 Apr;12(4):153-60. doi: http://dx.doi.org/10.13175/swjpcc021-16 PDF

Analysis of a Fatal Left Ventricular Assist Device Infection: A Case Report and Discussion

Neal Stuart Gerstein, MD FASE¹

Henry G. Chou, MD²

Andrew Lewis Dixon, MD¹

¹Department of Anesthesiology & Critical Care Medicine

University of New Mexico

Albuquerque, NM

²Department of Anesthesiology

Cedars-Sinai Medical Center

Los Angeles, CA

Introduction

Left ventricular assist device (VAD) therapy is an increasingly utilized treatment as a bridge to heart transplantation or as long-term destination therapy. Recent reports show there is a 22% - 32% incidence of VAD-associated infections with staphylococci and nosocomial gram-negative bacilli being the most common causative organisms (1,2). These organisms are often found in intensive care units, where they have the highest proportion of resistance, thus exposing already critically ill patients to the possibility of resistant organism VAD-associated infections (3). Mortality rates exceed 60% when sepsis develops in a patient with a continuous flow left VAD and infection is the number one cause of death in those awaiting cardiac transplantation (4,5). With continued left VAD use clinicians will likely see multidrug-resistant (MDR) or even pandrug-resistant organism VAD-associated infections. Clinicians need to be prepared to manage such an intimidating entity.

Case Report

We report a case of a 25 year-old male with a pandrug-resistant Pseudomonas aeruginosa VAD-associated infection. The patient’s medical history is significant for a diagnosis of idiopathic dilated cardiomyopathy refractory to maximal medical therapy requiring implantation of a HeartMate II (Thoratec Co., Pleasanton, CA, USA) continuous flow left VAD (Figure 1).

Figure 1. HeartMate II^® left VAD schematic (reprinted with the permission of Thoratec Co., Pleasanton, CA, USA).

His course was complicated with multiple hospital admissions for recurrent VAD-associated infections and numerous episodes of P. aeruginosa bacteremia that had been treated with a multitude of antipseudomonal antibiotics. He presented to our hospital for management of severe volume overload in the setting of VAD-associated infections. Transesophageal echocardiography demonstrated a left ventricular ejection fraction of 24% with severe left and right ventricular dilatation. Chest x-ray revealed cardiomegaly and multiple devices including the left VAD (Figure 2).

Figure 2. Chest X-ray demonstrating an enlarged cardiac silhouette, the HeartMate II axial pump (*) with inflow (down arrow, ↓) and outflow (up arrow, ↑) cannulas, biventricular pacer with leads in right atrium (A), coronary sinus (B), and right ventricle (C) (dashed arrows).

Blood cultures revealed MDR P. aeruginosa; except for showing intermediate sensitivity to tobramycin there was resistance to all antimicrobials tested. In vitro synergy testing revealed modest bacterial inhibition when only colistin, fosfomycin, imipenem, and tobramycin were combined. After maximizing medical therapy, multiple left VAD pocket washings and implantation of tobramycin beads followed. Intraoperative findings included an encapsulated infection around the driveline and obvious infection of the left VAD pocket. Repeat blood cultures showed P. aeruginosa had developed resistance to all antimicrobials including tobramycin. Subsequently the left VAD was explanted and the patient was transitioned to an extracorporeal membrane oxygenator (ECMO) in attempt to clear the infection. He was then transitioned to a TandemHeart (CardiacAssist Inc., Pittsburgh, PA, USA), a percutaneous LVAD, as he was not dependent on ECMO for oxygenation. He was able to clear the bacteremia after removal of the infected HeartMate II while on colistin, fosfomycin, tobramycin, azithromycin and rifampin, but was not able to clear the remaining left VAD pocket infection, which again spread systemically. Despite maximal medical and surgical interventions, he died from profound septic shock and multisystem organ failure. To date this is the first known case of a pandrug-resistant P. aeruginosa VAD-associated infection reported in the literature.

Discussion

P. aeruginosa organisms have intrinsic resistance to numerous broad spectrum antibiotics, and can easily develop acquired resistance to most if not all available antimicrobial agents (3). Risk factors for the development of pandrug-resistant P. aeruginosa include previous treatment with antipseudomonal antibiotics and prolonged treatment times. Given our patient had multiple P. aeruginosa infections, treated with multiple rounds of antipseudomonal antibiotics, it is not surprising that pandrug-resistance developed. Few therapeutic options are available for treatment and no new agents are available to evade the known resistance mechanisms. Treatment can be optimized using synergistic combination therapy, which may be the only medical management option in patients with pandrug-resistant P. aeruginosa infections. Some have suggested that rifampin in combination with colistin may be a promising approach (3). Some experts recommend in vitro synergy testing when an organism is resistant to currently recommended antibiotic regimens (6,7). However, a recent review of antibiotic therapy for gram-negative infections describes the utility of in vitro synergy testing equivocal in the context of Pseudomonas infection (8). We managed our patient with combination therapy; however, not until pandrug-resistant P. aeruginosa was isolated did we introduce rifampin in combination with colistin.

A recent review of VAD-associated infections showed the majority were managed without surgical intervention; only 13% required surgical debridement and only in cases of severe infection and/or failed conservative treatment was left VAD explantation required. Since this case there has been a proposed algorithm for management of VAD-associated infections (2); our management, though prior to published guidelines, was in step with the algorithm. Of note, there was no discussion of explanting an left VAD to ECMO to aid in clearing a resistant infection. We felt this was a rational option given our inability to clear the infection. It is unclear as to exactly why our patient was never able to fully clear his infection. Given the patient’s other pre-existing extensive cardiac hardware (i.e. implanted pacer), it is possible that he remained colonized even after maximal surgical and medical therapy. Though speculative, it is possible that removing all foreign material may have allowed for complete infection clearance.

Aside from aggressive medical and surgical management, systolic heart failure with VAD-associated infections may be effectively managed with heart transplantation (9). Our consensus was that this option was neither in the best interest of the patient nor the best use of available resources given the severity of his condition.

Conclusion

Clinicians will continue to see VAD-associated infections with resistant organisms. To minimize adverse outcomes, including VAD-associated infection, prudent patient selection and timing of VAD placement is paramount, as VAD’s placed in critically ill patients have been consistently associated with adverse outcomes (10).

References

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Reference as: Gerstein NS, Chou HG, Dixon AL. Analysis of a fatal left ventricular assist device infection: a case report and discussion. Southwest J Pulm Crit Care. 2015;10:16-20. doi: http://dx.doi.org/10.13175/swjpcc139-14 PDF