CASE REPORT
Methylene Blue for Acute Septic Cardiomyopathy in a Burned Patient Joseph J. Schlesinger, MD,*† and Christina F. Burger, PharmD, BCPS‡§
The objective of this case summary was to describe the use of methylene blue (MB) in a burned patient with acute septic cardiomyopathy. A 60-year-old Caucasian man was admitted to the Burn Intensive Care Unit with 45% TBSA burns after a house explosion. During the course of his care, he experienced hypotension that was refractory to fluid therapy and vasoactive medications. Echocardiography and right heart catheterization showed new acute systolic dysfunction with concurrent elevated systemic vascular resistance (SVR). High-dose inotropic agents did not improve cardiac function, and septic shock rendered him a poor candidate for mechanical intra-aortic balloon pump support. MB was administered to sensitize the myocardium to catecholamines and improve contractility with the goal of weaning the other vasoactive medications and diuresing for afterload reduction when hemodynamic stability was achieved. MB has been described in critical care medicine predominately for vasoplegia after cardiopulmonary bypass1–3 and vasodilatory septic shock.4,5 Our patient had acute septic cardiomyopathy that was refractory to standard pharmacologic approaches to inotropy with concurrent elevated SVR. Hypothesizing the differential temporal effect of inducible nitric oxide synthase on the vasculature and myocardium, we administered MB to improve contractility and support the impending vasodilatory effects of distributive shock. Although MB is not a new drug, the application for septic cardiomyopathy with a supranormal SVR is a unique application. Because of the risk profile associated with MB, we recommend drug monitoring utilizing serial echocardiography and/or right heart catheterization. (J Burn Care Res 2016;37:e287–e291)
Septic cardiomyopathy occurs because of the systemic inflammatory response that can result from both infectious and noninfectious etiologies, such as trauma, cardiopulmonary bypass, pancreatitis, ischemia–reperfusion injuries, or allograft rejection.6 The cytokines and proinflammatory mediators that are released during a time of severe stress can induce a dominant left ventricular heart failure and decreased cardiac output, which is often masked by a low systemic vascular From the *Division of Critical Care Medicine, Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tennessee; †Division of Critical Care Medicine, Department of Anesthesiology, University of Nairobi, Kenya; ‡Department of Pharmacy, Saint Thomas Rutherford Hospital, Murfreesboro, Tennessee and §Department of Clinical Pharmacy, University of Tennessee College of Pharmacy, Memphis, Tennessee. Address correspondence to: Joseph J. Schlesinger II, MD, Division of Critical Care Medicine, Department of Anesthesiology, Vanderbilt University Medical Center, 1211, 21st Avenue South, Medical Arts Building #526, Nashville, Tennessee 37212. E-mail: [email protected] Copyright © 2015 by the American Burn Association 1559-047X/2015 DOI: 10.1097/BCR.0000000000000237
resistance (SVR) resulting from sepsis-induced vasodilation.6 In this report, we describe the use of methylene blue (MB) to improve cardiac contractility and avert impending sepsis-induced vasodilation in a burn patient with septic cardiomyopathy. In addition, we present a unique monitoring technique for MB, which employees a combination of invasive monitoring in the form of pulmonary artery catheterization and minimally invasive monitoring in the form of continuous hemodynamic transesophageal echocardiography (hTEE) with the ImaCor© device (ImaCor, Inc., Garden City, NY).7–10
CASE REPORT A 60-year-old Caucasian man with a past medical history of paroxysmal atrial fibrillation was admitted to Vanderbilt University Medical Center’s Burn Intensive Care Unit (ICU) with a 45% TBSA burn after a house explosion. He arrived with peripheral intravenous (IV) access and was stable on supplemental oxygen. He became increasingly somnolent e287
Journal of Burn Care & Research May/June 2016
e288 Schlesinger and Burger
during the first hour of admission; central access was obtained, and the patient’s trachea was intubated. Crystalloid (Plasmalyte©, Baxter International, Deerfield, IL) was administered using the Parkland fluid resuscitation strategy11 to achieve a urine output of 1 ml/kg/hr: 4 ml/kg × body weight (kg) × %TBSA = total fluid volume (ml); 50% given during the first 8 hours, with the remainder given during the following 16 hours.11 A bronchoscopic exam was consistent with grade I (one) inhalation injury; his carboxyhemoglobin level was 8%. A cardiologist performed a baseline transthoracic echocardiogram (TTE), which yielded grade I diastolic dysfunction, ejection fraction of 55%, and no valvular pathology. The patient went to the operating room the next day for burn surgery and was extubated shortly after arriving back to the ICU. Thirty hours after admission, the patient’s oxygen requirement began to increase, and a lobar infiltrate consistent with pneumonia was demonstrated on chest radiography. Broad spectrum antibiotics were initiated, but the patient became hemodynamically unstable. Norepinephrine (5 μg/min initial rate, titrated to mean arterial pressure [MAP] greater than or equal to 65 mmHg) and vasopressin (0.04 units/min) infusions were administered along with fluid boluses of 500–1000 ml of crystalloid (Plasmalyte©). Despite receiving 15,300 ml of crystalloid from the Parkland resuscitation during the first 24 hours as well as additional fluid boluses, his urine output decreased to less than 0.5 ml/kg/hr, and he remained hypotensive. Approximately 48 hours after admission, an epinephrine infusion was started (2 μg/min initial rate, titrated to a MAP of greater than or equal to 65 mmHg). A pulmonary artery catheter was placed, revealing an initial cardiac index
(CI) of 0.9 L/min/m2, SVR of 2100 dynes seconds/ cm5, and mixed venous oxygen saturation (SVO2) of 23% (Table 1). A repeat TTE showed global hypokinesis with an ejection fraction of 10%, and a diagnosis of septic cardiomyopathy was made. Given that the patient had a known pneumonia and suspected bacteremia (blood cultures later revealed methicillin resistant Staphylococcus aureus and Klebsiella) and the profound nature of the septic cardiomyopathy with a nonischemic pattern on echocardiography, an IABP was not placed. Instead, an ImaCor© hTEE probe7–10 was placed and a milrinone infusion was started (0.375 μg/kg/min initial dose) for inotropic support. The hTEE probe was chosen because it is minimally invasive, the size of an orogastric tube. The probe provides views of the superior vena cava, a mid-esophageal four-chamber view, and a deep trans-gastric two-chamber view. This allows the clinician to assess volume status via a fractional percent change of the cardiac chambers and wall motion abnormalities.7–10 Milrinone was chosen over other inotropic agents, such as dobutamine because there was concern that the beta-agonism of dobutamine may precipitate atrial fibrillation with rapid ventricular rate given the patient’s history of paroxysmal atrial fibrillation.12 In the absence of acidemia, anemia, and hypovolemia as measured by continuous ImaCor© hTEE and serial TTE of the inferior vena cava, the underlying cause of the patient’s continued hypotension and poor CI was thought to be failed cardiac contractility.6 The ICU team hypothesized that the overwhelming bacterial endotoxin load from his pneumonia and suspected bacteremia activated inducible nitric oxide synthase (iNOS), leading to excessive production of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP).4,13–18 Although this phenomenon affects both the myocardium and vasculature, there appeared to be a
Table 1. Hemodynamic Parameters Before MB Administration and 6 Hours After MB Administration
Cardiac Index (CI) (L/min/m2) Systemic Vascular Resistance (SVR; dynes seconds/cm5) Mixed venous oxygen saturation (SVO2; %) Pulmonary Capillary Wedge Pressure (PCWP; mmHg) Pulmonary Artery Pressure (PAP; mmHg) PaO2/FiO2 ratio Norepinephrine dose (μg/min) Vasopressin dose (units/min) Milrinone dose (μg/kg/min) Epinephrine dose (μg/min)
2 Hours Before MB
Immediately Before MB
6 Hours After MB
1.1 1950
0.9 2100
2.7 1250
27 19
23 20
65 12
42/18 >300 18 0.04 0.375 2
45/21 >300 25 0.04 0.375 5
27/13 >300 7 0 0.25 0
Journal of Burn Care & Research Volume 37, Number 3
time separable component, causing cardiomyopathy with a compensatory, albeit unusually high, SVR in our burn patient. The ICU team felt that the vasculature would soon succumb to the deleterious effects of the pneumonia and bacteremia, and the patient would die without a drastic intervention. The decision was made to use MB with the goal of improving cardiac contractility and providing vasomotor tone to the vasculature as the endotoxemia started to take hold. One dose of MB 2 mg/kg IV was given over 60 minutes. Within 6 hours, the CI improved to 2.7 L/min/m2, the SVR improved to 1250 dynes seconds/cm5, and the SVO2 improved to 65% (Table 1). The vasoactive medications were weaned and a furosemide infusion was initiated for afterload reduction the following day. Within 48 hours of receiving MB, the patient was extubated on a low-dose milrinone infusion. The milrinone was weaned off over the next 24 hours, the patient was transferred to the burn step-down unit, and the remainder of his burn surgery was completed.
DISCUSSION MB is approved by the Food and Drug Administration for the treatment of drug-induced methemoglobinemia.19 It is also commonly used for unlabelled indications such as treatment of ifosfamide-induced encephalopathy,20,21 vasoplegia after cardiopulmonary bypass,1–3 and septic shock.4,5,13 Under normal physiologic conditions, l-arginine is converted to NO by a constitutive form of nitric oxide synthase (eNOS) that is present in the endothelium and regulated by negative feedback mechanisms.4,13 NO then activates the second messenger guanylate cyclase, which converts cyclic guanosine triphosphate (cGTP) to cGMP, resulting in smooth muscle relaxation and maintenance of normal vascular tone.4,13 In patients with septic shock, bacterial endotoxins and inflammatory cytokines can activate production of an inducible nitric oxide synthase (iNOS), present in both the vasculature and the myocardium, which is not responsive to negative feedback mechanisms.4,13–17 This uncontrolled synthesis of iNOS and excessive production of NO and cGMP lead to profound vasodilation, hyporeactivity to catecholamines/vasopressors, and decreased inotropy.4,13,17,18 MB acts to inhibit guanylate cyclase, eNOS, and iNOS; thereby normalizing concentrations of NO and cGMP.4,13 In patients with septic shock, inhibition of NO and cGMP overproduction results in increased MAP, improved cardiac contractility, and increased sensitivity to catecholamines in both the vasculature and myocardium.4,13 The
Schlesinger and Burger e289
mechanism of sensitizing the myocardium to catecholamines was the impetus for choosing MB to aid in the management of septic cardiomyopathy in this patient. There have been several case reports and studies demonstrating the use of MB in the treatment of septic shock but only two randomized controlled trials. Memis et al5 randomized 30 patients with severe sepsis to receive MB 0.5 mg/kg/hr IV for 6 hours or isotonic saline. Plasma concentrations of the inflammatory cytokines tumor necrosis factor-alpha, interleukin-1, interleukin-2, interleukin-6, and interleukin-8 were measured before and immediately after the infusion and at 24 and 48 hours after completion of the infusion. In this study, there was no difference in plasma cytokine levels between groups immediately after and at measured time points after completion of the infusion. Patients receiving MB had significantly higher MAP when compared with baseline and patients in the control group, but this difference was no longer present at 24 hours postinfusion. An increase in MAP was seen even in patients who were not vasopressor dependent. This study illustrates that MB exerts its positive effects through its alteration on hemodynamics, not on inflammatory cytokines. There were no significant differences between study groups in arterial blood gas measurements, Acute Physiology and Chronic Health Evaluation II scores, Sequential Organ Failure Assessment scores, or mortality. Kirov et al4 studied 20 patients admitted to the ICU with severe sepsis and septic shock. All patients had pulmonary catheters in place and received mechanical ventilation. Patients were excluded if they were less than 18 years of age, pregnant, receiving corticosteroids, immunosuppressants, or chemotherapy, or had a known irreversible underlying disease. Patients were randomized 1:1 to receive either isotonic saline or MB 2 mg/kg IV bolus over 15 minutes, followed 2 hours later by an infusion at increasing rates of 0.25, 0.5, 1, and 2 mg/kg/hr over 1 hour each. Protocols for adjustment of vasopressors were established before initiation of the study. At 6 and 24 hours, MB increased MAP compared with placebo. In addition, patients receiving MB required lower doses of vasopressors. Stroke volume index (SVI), left ventricular stroke work index (LVSWI), and right ventricular stroke work index (RVSWI) were preserved in the MB group, whereas they steadily declined in the placebo group. The declining SVI, LVSWI, and RVSWI in the control group reflect the progressive myocardial depression present in septic patients, whereas the improvement in these measurements in the MB group suggests
Journal of Burn Care & Research May/June 2016
e290 Schlesinger and Burger
that MB inhibits sepsis-induced cardiac dysfunction. There was no difference in clinical outcomes, such as length of stay, duration of shock or mechanical ventilation, or survivors at 28 days. No detrimental effects on gas exchange were observed. Several other studies have demonstrated MB’s effect on the myocardium. Although its effects are short lived (approximately 2–3 hours after a bolus and
Methylene Blue for Acute Septic Cardiomyopathy in a Burned Patient Joseph J. Schlesinger, MD,*† and Christina F. Burger, PharmD, BCPS‡§
The objective of this case summary was to describe the use of methylene blue (MB) in a burned patient with acute septic cardiomyopathy. A 60-year-old Caucasian man was admitted to the Burn Intensive Care Unit with 45% TBSA burns after a house explosion. During the course of his care, he experienced hypotension that was refractory to fluid therapy and vasoactive medications. Echocardiography and right heart catheterization showed new acute systolic dysfunction with concurrent elevated systemic vascular resistance (SVR). High-dose inotropic agents did not improve cardiac function, and septic shock rendered him a poor candidate for mechanical intra-aortic balloon pump support. MB was administered to sensitize the myocardium to catecholamines and improve contractility with the goal of weaning the other vasoactive medications and diuresing for afterload reduction when hemodynamic stability was achieved. MB has been described in critical care medicine predominately for vasoplegia after cardiopulmonary bypass1–3 and vasodilatory septic shock.4,5 Our patient had acute septic cardiomyopathy that was refractory to standard pharmacologic approaches to inotropy with concurrent elevated SVR. Hypothesizing the differential temporal effect of inducible nitric oxide synthase on the vasculature and myocardium, we administered MB to improve contractility and support the impending vasodilatory effects of distributive shock. Although MB is not a new drug, the application for septic cardiomyopathy with a supranormal SVR is a unique application. Because of the risk profile associated with MB, we recommend drug monitoring utilizing serial echocardiography and/or right heart catheterization. (J Burn Care Res 2016;37:e287–e291)
Septic cardiomyopathy occurs because of the systemic inflammatory response that can result from both infectious and noninfectious etiologies, such as trauma, cardiopulmonary bypass, pancreatitis, ischemia–reperfusion injuries, or allograft rejection.6 The cytokines and proinflammatory mediators that are released during a time of severe stress can induce a dominant left ventricular heart failure and decreased cardiac output, which is often masked by a low systemic vascular From the *Division of Critical Care Medicine, Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tennessee; †Division of Critical Care Medicine, Department of Anesthesiology, University of Nairobi, Kenya; ‡Department of Pharmacy, Saint Thomas Rutherford Hospital, Murfreesboro, Tennessee and §Department of Clinical Pharmacy, University of Tennessee College of Pharmacy, Memphis, Tennessee. Address correspondence to: Joseph J. Schlesinger II, MD, Division of Critical Care Medicine, Department of Anesthesiology, Vanderbilt University Medical Center, 1211, 21st Avenue South, Medical Arts Building #526, Nashville, Tennessee 37212. E-mail: [email protected] Copyright © 2015 by the American Burn Association 1559-047X/2015 DOI: 10.1097/BCR.0000000000000237
resistance (SVR) resulting from sepsis-induced vasodilation.6 In this report, we describe the use of methylene blue (MB) to improve cardiac contractility and avert impending sepsis-induced vasodilation in a burn patient with septic cardiomyopathy. In addition, we present a unique monitoring technique for MB, which employees a combination of invasive monitoring in the form of pulmonary artery catheterization and minimally invasive monitoring in the form of continuous hemodynamic transesophageal echocardiography (hTEE) with the ImaCor© device (ImaCor, Inc., Garden City, NY).7–10
CASE REPORT A 60-year-old Caucasian man with a past medical history of paroxysmal atrial fibrillation was admitted to Vanderbilt University Medical Center’s Burn Intensive Care Unit (ICU) with a 45% TBSA burn after a house explosion. He arrived with peripheral intravenous (IV) access and was stable on supplemental oxygen. He became increasingly somnolent e287
Journal of Burn Care & Research May/June 2016
e288 Schlesinger and Burger
during the first hour of admission; central access was obtained, and the patient’s trachea was intubated. Crystalloid (Plasmalyte©, Baxter International, Deerfield, IL) was administered using the Parkland fluid resuscitation strategy11 to achieve a urine output of 1 ml/kg/hr: 4 ml/kg × body weight (kg) × %TBSA = total fluid volume (ml); 50% given during the first 8 hours, with the remainder given during the following 16 hours.11 A bronchoscopic exam was consistent with grade I (one) inhalation injury; his carboxyhemoglobin level was 8%. A cardiologist performed a baseline transthoracic echocardiogram (TTE), which yielded grade I diastolic dysfunction, ejection fraction of 55%, and no valvular pathology. The patient went to the operating room the next day for burn surgery and was extubated shortly after arriving back to the ICU. Thirty hours after admission, the patient’s oxygen requirement began to increase, and a lobar infiltrate consistent with pneumonia was demonstrated on chest radiography. Broad spectrum antibiotics were initiated, but the patient became hemodynamically unstable. Norepinephrine (5 μg/min initial rate, titrated to mean arterial pressure [MAP] greater than or equal to 65 mmHg) and vasopressin (0.04 units/min) infusions were administered along with fluid boluses of 500–1000 ml of crystalloid (Plasmalyte©). Despite receiving 15,300 ml of crystalloid from the Parkland resuscitation during the first 24 hours as well as additional fluid boluses, his urine output decreased to less than 0.5 ml/kg/hr, and he remained hypotensive. Approximately 48 hours after admission, an epinephrine infusion was started (2 μg/min initial rate, titrated to a MAP of greater than or equal to 65 mmHg). A pulmonary artery catheter was placed, revealing an initial cardiac index
(CI) of 0.9 L/min/m2, SVR of 2100 dynes seconds/ cm5, and mixed venous oxygen saturation (SVO2) of 23% (Table 1). A repeat TTE showed global hypokinesis with an ejection fraction of 10%, and a diagnosis of septic cardiomyopathy was made. Given that the patient had a known pneumonia and suspected bacteremia (blood cultures later revealed methicillin resistant Staphylococcus aureus and Klebsiella) and the profound nature of the septic cardiomyopathy with a nonischemic pattern on echocardiography, an IABP was not placed. Instead, an ImaCor© hTEE probe7–10 was placed and a milrinone infusion was started (0.375 μg/kg/min initial dose) for inotropic support. The hTEE probe was chosen because it is minimally invasive, the size of an orogastric tube. The probe provides views of the superior vena cava, a mid-esophageal four-chamber view, and a deep trans-gastric two-chamber view. This allows the clinician to assess volume status via a fractional percent change of the cardiac chambers and wall motion abnormalities.7–10 Milrinone was chosen over other inotropic agents, such as dobutamine because there was concern that the beta-agonism of dobutamine may precipitate atrial fibrillation with rapid ventricular rate given the patient’s history of paroxysmal atrial fibrillation.12 In the absence of acidemia, anemia, and hypovolemia as measured by continuous ImaCor© hTEE and serial TTE of the inferior vena cava, the underlying cause of the patient’s continued hypotension and poor CI was thought to be failed cardiac contractility.6 The ICU team hypothesized that the overwhelming bacterial endotoxin load from his pneumonia and suspected bacteremia activated inducible nitric oxide synthase (iNOS), leading to excessive production of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP).4,13–18 Although this phenomenon affects both the myocardium and vasculature, there appeared to be a
Table 1. Hemodynamic Parameters Before MB Administration and 6 Hours After MB Administration
Cardiac Index (CI) (L/min/m2) Systemic Vascular Resistance (SVR; dynes seconds/cm5) Mixed venous oxygen saturation (SVO2; %) Pulmonary Capillary Wedge Pressure (PCWP; mmHg) Pulmonary Artery Pressure (PAP; mmHg) PaO2/FiO2 ratio Norepinephrine dose (μg/min) Vasopressin dose (units/min) Milrinone dose (μg/kg/min) Epinephrine dose (μg/min)
2 Hours Before MB
Immediately Before MB
6 Hours After MB
1.1 1950
0.9 2100
2.7 1250
27 19
23 20
65 12
42/18 >300 18 0.04 0.375 2
45/21 >300 25 0.04 0.375 5
27/13 >300 7 0 0.25 0
Journal of Burn Care & Research Volume 37, Number 3
time separable component, causing cardiomyopathy with a compensatory, albeit unusually high, SVR in our burn patient. The ICU team felt that the vasculature would soon succumb to the deleterious effects of the pneumonia and bacteremia, and the patient would die without a drastic intervention. The decision was made to use MB with the goal of improving cardiac contractility and providing vasomotor tone to the vasculature as the endotoxemia started to take hold. One dose of MB 2 mg/kg IV was given over 60 minutes. Within 6 hours, the CI improved to 2.7 L/min/m2, the SVR improved to 1250 dynes seconds/cm5, and the SVO2 improved to 65% (Table 1). The vasoactive medications were weaned and a furosemide infusion was initiated for afterload reduction the following day. Within 48 hours of receiving MB, the patient was extubated on a low-dose milrinone infusion. The milrinone was weaned off over the next 24 hours, the patient was transferred to the burn step-down unit, and the remainder of his burn surgery was completed.
DISCUSSION MB is approved by the Food and Drug Administration for the treatment of drug-induced methemoglobinemia.19 It is also commonly used for unlabelled indications such as treatment of ifosfamide-induced encephalopathy,20,21 vasoplegia after cardiopulmonary bypass,1–3 and septic shock.4,5,13 Under normal physiologic conditions, l-arginine is converted to NO by a constitutive form of nitric oxide synthase (eNOS) that is present in the endothelium and regulated by negative feedback mechanisms.4,13 NO then activates the second messenger guanylate cyclase, which converts cyclic guanosine triphosphate (cGTP) to cGMP, resulting in smooth muscle relaxation and maintenance of normal vascular tone.4,13 In patients with septic shock, bacterial endotoxins and inflammatory cytokines can activate production of an inducible nitric oxide synthase (iNOS), present in both the vasculature and the myocardium, which is not responsive to negative feedback mechanisms.4,13–17 This uncontrolled synthesis of iNOS and excessive production of NO and cGMP lead to profound vasodilation, hyporeactivity to catecholamines/vasopressors, and decreased inotropy.4,13,17,18 MB acts to inhibit guanylate cyclase, eNOS, and iNOS; thereby normalizing concentrations of NO and cGMP.4,13 In patients with septic shock, inhibition of NO and cGMP overproduction results in increased MAP, improved cardiac contractility, and increased sensitivity to catecholamines in both the vasculature and myocardium.4,13 The
Schlesinger and Burger e289
mechanism of sensitizing the myocardium to catecholamines was the impetus for choosing MB to aid in the management of septic cardiomyopathy in this patient. There have been several case reports and studies demonstrating the use of MB in the treatment of septic shock but only two randomized controlled trials. Memis et al5 randomized 30 patients with severe sepsis to receive MB 0.5 mg/kg/hr IV for 6 hours or isotonic saline. Plasma concentrations of the inflammatory cytokines tumor necrosis factor-alpha, interleukin-1, interleukin-2, interleukin-6, and interleukin-8 were measured before and immediately after the infusion and at 24 and 48 hours after completion of the infusion. In this study, there was no difference in plasma cytokine levels between groups immediately after and at measured time points after completion of the infusion. Patients receiving MB had significantly higher MAP when compared with baseline and patients in the control group, but this difference was no longer present at 24 hours postinfusion. An increase in MAP was seen even in patients who were not vasopressor dependent. This study illustrates that MB exerts its positive effects through its alteration on hemodynamics, not on inflammatory cytokines. There were no significant differences between study groups in arterial blood gas measurements, Acute Physiology and Chronic Health Evaluation II scores, Sequential Organ Failure Assessment scores, or mortality. Kirov et al4 studied 20 patients admitted to the ICU with severe sepsis and septic shock. All patients had pulmonary catheters in place and received mechanical ventilation. Patients were excluded if they were less than 18 years of age, pregnant, receiving corticosteroids, immunosuppressants, or chemotherapy, or had a known irreversible underlying disease. Patients were randomized 1:1 to receive either isotonic saline or MB 2 mg/kg IV bolus over 15 minutes, followed 2 hours later by an infusion at increasing rates of 0.25, 0.5, 1, and 2 mg/kg/hr over 1 hour each. Protocols for adjustment of vasopressors were established before initiation of the study. At 6 and 24 hours, MB increased MAP compared with placebo. In addition, patients receiving MB required lower doses of vasopressors. Stroke volume index (SVI), left ventricular stroke work index (LVSWI), and right ventricular stroke work index (RVSWI) were preserved in the MB group, whereas they steadily declined in the placebo group. The declining SVI, LVSWI, and RVSWI in the control group reflect the progressive myocardial depression present in septic patients, whereas the improvement in these measurements in the MB group suggests
Journal of Burn Care & Research May/June 2016
e290 Schlesinger and Burger
that MB inhibits sepsis-induced cardiac dysfunction. There was no difference in clinical outcomes, such as length of stay, duration of shock or mechanical ventilation, or survivors at 28 days. No detrimental effects on gas exchange were observed. Several other studies have demonstrated MB’s effect on the myocardium. Although its effects are short lived (approximately 2–3 hours after a bolus and
![[Acute upper limb embolism in a severely burned patient].](/assets/img/hold.png)
