Article, Emergency Medicine

Endotoxin adsorption by polymyxin B column or intraaortic balloon pumping use for severe septic cardiomyopathy

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American Journal of Emergency Medicine

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American Journal of Emergency Medicine 31 (2013) 893.e1-893.e3

Endotoxin adsorption by polymyxin B column or intraaortic balloon pumping use for severe septic cardiomyopathy?

Abstract

Septic patients often have low cardiac output. Some of them present severe cardiac dysfunction such as septic cardiomyopathy. However, no well-known and effective treatment for septic cardiomyopathy exists. The effect of endotoxin adsorption by polymyxin B-immobilized fiber column-direct hemoperfusion (PMX-DHP) and intraaortic balloon pumping (IABP) for septic shock remains uncertain. We experienced 2 very contrastive case reports of severe septic cardiomyopathy. We experienced 2 cases of severe septic cardiomyopathy with refractory shock. Case 1 with colon perforation presented refractory shock 6 hours after PMX-DHP, and IABP immediately improved her hemodynamics. In contrast, IABP had no effect at all in case 2 with viral enteritis, but PMX- DHP improved her blood pressure and stroke volume markedly. The probability of impaired coronary microcirculation and relative brady- cardia is the least required conditions for IABP use in severe septic cardiomyopathy. Meanwhile, PMX-DHP could be a good option for septic cardiomyopathy because of its fewer complications.

Septic cardiomyopathy is a cardiac dysfunction that occurs in a septic condition. One quarter of sepsis patients have decreased cardiac output [1,2]. Relative decrease of cardiac output is reportedly observed in 83% of septic Multiple organ dysfunction syndrome, and severe cardiac dysfunction, in 17% [3]. Septic cardiomyopathy is a myocardial disorder with no obvious ischemia or myocarditis. Although multiple mechanisms have been assumed, they have not been clarified clearly [4]. stress-induced cardiomyopathy or takotsubo cardiomyopathy, which is left ventricular apical ballooning in typical cases induced by psychologic and physical stresses or hypercatecho- laminemia, is a conceptually similar disease. Actually, apical balloon- ing was observed most in septic patients in medical Intensive care units [5]. However, the patterns of affected regions are different in different cases, and cases with midventricular, basal portion, and diffuse regions exist [6].

What is the treatment or appropriate management for severe septic cardiomyopathy? Inotropic catecholamines such as dobuta- mine are difficult to use because of the base of hypercatecholamine- mia. No recommendable treatment exists to manage the circulation [4]. If septic cardiomyopathy once presents cardiogenic refractory shock despite of usual septic managements, the strategies for pressure rising were limited, intraaortic balloon pumping (IABP) and blood purification including endotoxin adsorption by polymyxin B-immo- bilized fiber column-direct hemoperfusion (PMX-DHP) in Japan. Intraaortic balloon pumping is a very effective management therapy

? The work was performed at the Intensive Care Unit of the Tokyo University Hospital.

0735-6757/$ – see front matter (C) 2013

in usual stress-induced cardiomyopathy. However, it remains ques- tionable whether IABP is effective in a septic condition, irrespective of whether IABP acts to increase or decrease blood pressure. Several studies for IABP in the experimental sepsis models have been reported; however, its efficacy remains controversial [7-9]. Polymyx- in B-immobilized fiber column-direct hemoperfusion might be effective both for vascular resistance and heart contraction in some septic cardiomyopathy. However, there is no report in which PMX- DHP was used for typical septic cardiomyopathy.

As described herein, we experienced 2 very contrastive cases of septic cardiomyopathy. In case 1 with refractory shock 6 hours after PMX-DHP, IABP was much effective for the increase of blood pressure. However, IABP had no effect in case 2, and PMX-DHP was markedly effective. We discussed the difference between these 2 cases.

A 74-year-old woman presented with septic shock from general- ized peritonitis with perforation of the sigmoid colon by colonoscopy. Her medical history included hypertension and Femoral neck fracture. On admission, she presented with pancytopenia, white blood cell count of 800/uL, hemoglobin level of 9.6 g/dL, and platelet count of 9.6

x 104/uL, which later turned out to be multiple myeloma Bence-Jones

Protein immunoglobulin G-? type. Total protein was 10.1 g/dL. Emergency surgery was urgently performed for irrigation of the peritoneal cavity and loop colostomy of sigmoid colon. After surgery, she was admitted to the ICU with mechanical ventilation and PMX- DHP was immediately performed. At 6 hours after termination of PMX- DHP, she abruptly became refractory septic and cardiogenic shock, nonresponsive to Fluid loading and catecholamines. Her cardiac function was decreased critically, severely worse than before surgery. The ejection fraction was 35.3%, diffuse hypokinesis in echocardiog- raphy. Pulmonary artery catheter analysis revealed a cardiac index (CI) of 1.45 mL/min/min2 and heart rate (HR) of 125 per minute. Brain natriuretic peptide was 1717.6 pg/mL, and lactate was 6.5 mmol/L. Creatine kinase-MB was negative. Because her condition continued to worsen and no other treatment was left, we decided the indication of IABP at bedside. After activation of IABP at a frequency of 1:1, her hemodynamic status improved immediately (Fig. A). Her CI and mean arterial pressure (MAP) markedly increased, and HR gradually decreased. She recovered subsequently. Polymyxin B-immobilized fiber column-direct hemoperfusion was performed again on the next day and withdrew from IABP 2 days later, without any complication. Later, coronary angiography was performed, but no Significant stenosis was observed. She was discharged on foot.

A healthy 19-year-old woman presented with 40?C fever, abdominal

pain, nausea, and water diarrhea. Although it was flu season, repeated influenza Antigen tests and polymerase chain reaction were negative. White blood cell count of 10900/uL, C-reactive reaction of 28 mg/dL, but

893.e2 K. Nakamura et al. / American Journal of Emergency Medicine 31 (2013) 893.e1893.e3

Fig. Clinical course. DOB, dobutamine; NoA, noradrenaline; SV, stroke volume. A, Case 1 was a 74-year-old woman with peritonitis from perforation of the sigmoid colon. Six hours after PMX-DHP, she abruptly became refractory septic and cardiogenic shock. Her CI was 1.45 mL/min/min2. She was nonresponsive to fluid loading and catecholamine. Intraaortic balloon pumping at a frequency of 1:1 was indicated. Then her blood pressure became elevated immediately via increased cardiac output. B, Case 2 was a healthy 19-year-old woman with viral enteritis. One day after admission, she presented with Refractory septic shock and pulmonary edema. Her CI was 3.21 mL/min/m2. Fluid load, catecholamine, and milrinone had no effect. Then IABP was started. However, her hemodynamics did not change. After PMX-DHP, her blood pressure and cardiac output were increased markedly.

all examinations for infection, including viral infection, and autoimmune antibody were negative on admission. Contrast-enhanced computed tomography showed whole bowel inflammation and edema and little ascites. Regarded as viral enteritis, oceltamivir and piperacillin/ tazobactam were given. One day after admission, she presented with septic shock and pulmonary edema. She was intubated and admitted into the ICU. Despite much fluid loading and catecholamine use, her blood pressure was not elevated. Echography revealed severe diffuse hypokinesis of the left ventricle, with an ejection fraction of 32.1%. Pulmonary artery catheter analysis revealed CI of 2.96 mL/min/m2 and HR of 158 per minute. Lactate was 1.6 mmol/L, and creatine kinase-MB was negative. Coronary angiography was performed, but no significant stenosis was observed and IABP was started. However, no change in hemodynamics was observed (Fig. B). Intraaortic balloon pumping did not match her heart rhythm effectively because of sinus tachycardia and sinus arrhythmia, and IABP acted at the frequency of 1:2. Then, PMX- DHP was performed. After PMX-DHP was started, her hemodynamics improved immediately and drastically (Fig. B). Heart contraction was improved to the ejection fraction of 72% at 1 day after PMX-DHP. Polymyxin B-immobilized fiber column-direct hemoperfusion was performed on 2 consecutive days. Intraaortic balloon pumping was weaned gradually off 4 days after indication. She recovered gradually and was discharged on foot.

Intraaortic balloon pumping was markedly effective for refractory

septic shock with cardiomyopathy in case 1 and provided her rising blood pressure, but not at all in case 2. Alternatively, PMX-DHP was markedly effective. No significant coronary stenosis was observed using coronary angiography in either case. What was the difference between the 2 cases in terms of the outcome?

Intraaortic balloon pumping has many complications as shortcom- ings such as a decrease in platelets [10], bleeding, embolism, lower extremity ischemia, renal dysfunction, and vessel injury [11]. Because these complications are extremely disadvantageous in a septic condition, IABP use for septic cardiomyopathy should be limited. The efficacy of IABP was demonstrated originally with randomized control trials for heart failure from myocardial infarction [12] or perioperative use for cardiac surgery [13]. Moreover, not all cardiogenic shock with myocardial infarction can benefit from IABP [14,15]. Intraaortic balloon pumping use for septic cardiomyopathy with no coronary stenosis, as in these 2 cases, should be carefully indicated.

Intraaortic balloon pumping fundamentally affects blood pressure by 2 processes: systolic unloading and diastolic augmentation. Therefore, it

is not clear how to affect overall blood pressure as MAP. Two recent animal studies for IABP showed different outcomes of MAP. Mean arterial pressure was increased with CI elevation in severe septic cardiomyopathy model [9]. However, MAP was even decreased with IABP in the other study in which CI was not changed [8]. Mean arterial pressure might decrease with IABP when CI was not elevated. Actually, marked elevation of CI was observed in case 1, but not in case 2. Intraaortic balloon pumping is expected to be effective only for cases in which cardiac output elevation can be anticipated via increased coronary perfusion from diastolic augmentation. Although no significant stenosis was observed, impairment of coronary microcirculation might have occurred in case 1, exacerbated by older age, disseminated intravascular coagulopathy, and high viscosity with hypergammaglobulinemia from multiple myeloma. High viscosity decreases the Coronary blood flow [16] and decreases CI [17]. The factors for impairments of microcirculation should be considered for IABP indication, in addition to ischemic heart disease.

In addition, the initial heart rate differed substantially in 2 cases. Case 1 presented relative bradycardia, HR of 125 per minute, and even lower after IABP activation, although initial HR was 158 per minute in case 2. In prominent tachycardia from sepsis, with sinus arrhythmia, IABP cannot synchronize and act effectively especially at a frequency of 1:1. Relative bradycardia is a required condition of IABP use for septic cardiomyopathy.

On the other hand, PMX-DHP, the blood purification with endotoxin and inflammatory mediator adsorption used in Japan for refractory septic shock [18,19], could be effective for severe septic cardiomyopathy. Because various inflammatory cytokines and hypercatecholaminemia are assumed to produce harmful effects and causes in cardiomyopathy, inflammatory mediator adsorption with PMX-DHP might improve septic cardiomyopathy fundamentally. One case report in Japan described that severe septic cardiomyopathy was rescued with multimodality therapy including PMX-DHP [20].

Polymyxin B-immobilized fiber column-direct hemoperfusion was markedly effective in our case 2, whereas IABP was not. Polymyxin B-immobilized fiber column-direct hemoperfusion would be possibly effective, regardless of patient’s HR and whether the impairments of microcirculation existed. Moreover, PMX-DHP has much fewer complications than IABP. Therefore, PMX-DHP can be considered as one treatment option for severe septic cardiomyopathy. In case 1, IABP was performed because PMX-DHP had been used 6 hours before shock onset. It was uncertain that PMX-DHP was effective or not in case 1 septic cardiomyopathy. Too early use of PMX-

K. Nakamura et al. / American Journal of Emergency Medicine 31 (2013) 893.e1893.e3 893.e3

DHP might matter, such as the case 1 with colon perforation who did not yet present septic shock.

In severe septic cardiomyopathy, PMX-DHP would be one of effective treatment options. Intraaortic balloon pumping would be also effective only when the probability of impairment of coronary microcirculation and relative bradycardia existed; however, it should be carefully indicated because of its complications.

Kensuke Nakamura MD

Department of Emergency and Critical Care Medicine

The University of Tokyo Hospital Tokyo 113-8655, Japan

E-mail address: [email protected]

Kent Doi MD

Department of Emergency and Critical Care Medicine

The University of Tokyo Hospital Tokyo 113-8655, Japan

Department of Hemodialysis and Apheresis The University of Tokyo Hospital Tokyo 113-8655, Japan

Ryota Inokuchi MD Tatsuma Fukuda MD Takahiro Hiruma MD Takeshi Ishii MD Susumu Nakajima MD

Department of Emergency and Critical Care Medicine

The University of Tokyo Hospital Tokyo 113-8655, Japan

Eisei Noiri MD Department of Hemodialysis and Apheresis The University of Tokyo Hospital

Tokyo 113-8655, Japan

Naoki Yahagi MD

Department of Emergency and Critical Care Medicine

The University of Tokyo Hospital Tokyo 113-8655, Japan

http://dx.doi.org/10.1016/j.ajem.2012.12.042

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