Author Response.

How to cite this article: Rajbanshi LK, Arjyal B. Author Response. Indian J Crit Care Med 2024;28(1):90-91.

Minoxidil Poisoning: A Case of Refractory Shock with Remarkable ECG Changes.

How to cite this article: Dash S, Sashindran VK. Minoxidil Poisoning: A Case of Refractory Shock with Remarkable ECG Changes. Indian J Crit Care Med 2023;27(9):688-689.

Harmonizing the Septic Shock Terminology: Need of the Hour.

How to cite this article: Magoon R, Puri S, Bandyopadhyay A. Harmonizing the Septic Shock Terminology: Need of the Hour. Indian J Crit Care Med 2023;27(4):294-295.

Can Use of Intravenous Methylene Blue Improve the Hemodynamics and Outcome of the Patients with Refractory Septic Shock? An Observational Study.

Introduction: Refractory shock, which fails to respond to conventional vasopressor therapy, is a common complication of sepsis. Methylene blue has emerged as a potential adjunctive treatment option for reversing refractory shock in sepsis. The aim of this study was to evaluate the impact of intravenous methylene blue infusion on hemodynamic improvement and mortality in patients with refractory shock. Methodology: This was an observational prospective study for the duration of six months conducted at intensive care a medical college and teaching hospital including 76 patients with a diagnosis of septic shock requiring vasopressor therapy. Intravenous (IV) methylene blue was infused as a bolus dose with 2 mg/kg dose in 20 minutes and its response to mean arterial blood pressure, decrease in vasopressor therapy, lactate level, and urine output was recorded in next 2 hours. Patients with improvement in mean arterial pressure (MAP) by 10% or decrease in vasopressor therapy in the next 2 hours were leveled as responder. The length of intensive care unit (ICU) stay, duration of mechanical ventilation, incidence of acute kidney injury (AKI), and mortality were compared between responder and non-responder. Results: A total of 76 patients with refractory shock were included in the study. With the use of IV methylene blue, 41 (53.9%) patients showed significant improvement in MAP within 2 hours (70.17 ± 8.30 vs 64.28 ± 11.84, p = 0.005). Responders were 4.019 times more likely to have vasopressor-free time within 24 hours (18.4% vs 5.3%, p = 0.020, odds ratio 4.019, 95% confidence interval, 1.180-13.682). However, there was no significant difference in terms of mortality, length of ICU stay, ventilator free days, and incidence of AKI. In the responder group, there was a significant increase in the MAP and decrease in vasopressor requirement pre- and post-infusion of methylene blue (p < 0.05). Responder had shorter vasopressor-free days as compared with non-responder (5.34 vs 6.79, p = 0.008) while the mean survival time was longer with responders (21.97 vs 15.93 days, p = 0.024). Conclusion: The use of IV methylene blue in refractory shock as an adjuvant therapy significantly improved the mean arterial blood pressure and decreased the requirement of vasopressor therapy as well as improvement in the survival time. However, there was no change in the mortality, length of ICU stay, ventilator-free days, or incidence of AKI in the patients. How to cite this article: Rajbanshi LK, Bajracharya A, Arjyal B, Devkota D. Can Use of Intravenous Methylene Blue Improve the Hemodynamics and Outcome of the Patients with Refractory Septic Shock? An Observational Study. Indian J Crit Care Med 2023;27(9):669-674.

[Application of extracorporeal membrane oxygenation technique in patients with refractory shock caused by dichlorvos poisoning].

Dichlorvos poisoning can cause muscarinic (M) -like symptoms, nicotinoid (N) -like symptoms and central nervous system manifestations. When severe poisoning is combined with refractory shock, the mortality rate exceeds 60%. At present, there are more and more studies on ECMO for poisoning, but there is no report on ECMO for treating refractory hypotension caused by dichlorvos poisoning. We analyzed 3 successful cases of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in the treatment of refractory shock caused by acute severe dichlorvos poisoning to explore the effectiveness of VA-ECMO in patients with severe poisoning.

A Multicenter Observational Cohort Study of Angiotensin II in Shock.

INTRODUCTION: Angiotensin II (Ang-2) is a non-catecholamine vasopressor that targets the renin-angiotensin-aldosterone system by agonism of the angiotensin type 1 receptor. Its utility as a vasopressor and a catecholamine-sparing agent was demonstrated in the pivotal ATHOS-3 trial, and numerous post-hoc analyses have shown reduced mortality in certain subsets of the population. METHODS: Consecutive adult patients at 5 centers who received Ang-2 from 2017-2020 were included in this multicenter, retrospective observational cohort study. Patient demographics, hemodynamics, and adverse events were collected. The primary outcomes of the study were the mean difference in MAP and norepinephrine (NEpi)-equivalent dose at hours 0 and 3 following initiation of Ang-2 therapy. RESULTS: One hundred and sixty-two patients were included in this study. The primary outcomes of an increase in MAP (mean difference 9.3 mmHg, 95% CI 6.4-12.1, p < 0.001) and a reduction in NEpi equivalent dose (mean difference 0.16 µg/kg/min, 95% CI 0.10-0.22, p < 0.001) between hours 0 and 3 were statistically significant. The median time to reach a MAP ≥65 was 16 minutes (IQR 5-60 min). After stratifying patients by the NED dose and number of vasopressors administered prior to the initiation of Ang-2, those with a NED dose < 0.2 µg/kg/min, NED dose < 0.3 µg/kg/min, or those on ≤ 3 vasopressors had a significantly greater reduction in NED by hour 3 than those patients above these thresholds. CONCLUSION: Ang-2 is an effective vasopressor and reduces catecholamine dose significantly. Its effect is rapid, with target MAP obtained within 30 minutes in most patients. Given the critical importance of adequate blood pressure to organ perfusion, Ang-2 should be considered when target MAP cannot be achieved with conventional vasopressors. Ang-2 should be utilized early in the course of shock, before the NED dose exceeds 0.2-0.3 µg/kg/min and before the initiation of the fourth-line vasopressor.

Dual veno-arterial extra-corporeal membrane oxygenation support in a patient with refractory hyperdynamic septic shock: a case report.

The hypodynamic septic shock appears to be a promising indication to veno-arterial membrane oxygenation (VA-ECMO) support of a patient with insufficient cardiac output. With cardiac recovery most of those patients progress into a hyperdynamic septic shock with cardiac output, which may not match critically low systemic vascular resistance to maintain perfusion pressures. Such refractory distributive shock represents a challenging indication to VA-ECMO. We report a rare case of a 27-year old patient who developed severe refractory hypodynamic septic shock due to the bilateral staphylococcal pneumonia and had to be initially rescued by femoro-femoral VA-ECMO. Despite extensive measures, he remained in intractable hypotension and profound tissue hypoperfusion with imminent multiorgan failure. The commencement of a second jugulo-axillary VA ECMO secured a total blood flow of 14.3 L/min, which restored perfusion pressure and successfully bridged patient over the period of critical haemodynamic instability and ultimately may have facilitated recovery.

Rescue therapy with intravenous immunoglobulin in severe refractory dengue: A pilot study.

Background: Severe dengue causes more than 22,000 deaths annually worldwide. Complicated dengue has high mortality of 44-72%. Disordered immune system with capillary leak and thrombocytopenia are hallmark of complicated dengue. Intravenous immunoglobulin (IV Ig) therapy has shown to be effective in complicated dengue in pediatric age group with refractory shock, but studies in adults are lacking. Its immunoresuscitative role is not yet fully explored in critically ill patients with severe dengue. Methods: This is retrospective observational study of patients with complicated dengue fever who were administered IV Ig therapy in a tertiary care hospital of southern India from 01 Jan 2018 to 31 Dec 2019. Results: A total of 999 patients with dengue were admitted; 754 (75.47%) were males, and 245 (24.53%) were females. A total of 402 (40.24%) patients presented with warning signs. Bleeding was seen in 121 patients (12.11%); 102 (10.21%) had shock; 29 (2.90%) had acute kidney injury and 24 (2.40%) had adult respiratory distress syndrome. Overall, four people died (mortality rate: 0.40%). IV Ig in the dose of 0.4 g/kg for 5 days was used in 13 critically ill patients where standard therapy failed, 9 patients with refractory shock (which included three with myocarditis with refractory shock), 2 with encephalitis, 2 in hemophagocytic lymphohistiocytosis. Two patients died, one with myocarditis with refractory shock and another with refractory shock. Conclusion: IV Ig therapy in critically ill patients with complicated dengue can be used as a rescue therapy.

[Value of functional echocardiographic parameters in predicting refractory septic shock in neonates]. / åŠŸèƒ½æ€§è¶ å£°å¿ƒåŠ¨å›¾å‚æ•°åœ¨æ–°ç”Ÿå„¿è„“æ¯’ç—‡ä¼‘å ‹ä¸­çš„ä¸´åºŠåº”ç”¨ä»·å€¼.

OBJECTIVES: To study the value of functional echocardiographic parameters in predicting refractory septic shock in neonates. METHODS: A total of 72 neonates with septic shock were enrolled. According to the highest value of septic shock score, they were divided into two groups: refractory (n=30) and non-refractory (n=42). The two groups were compared in terms of clinical data, laboratory findings, and functional echocardiographic parameters. The receiver operating characteristic (ROC) curve was used to evaluate the performance of functional echocardiographic parameters in predicting refractory septic shock. RESULTS: Compared with the non-refractory group, the refractory group had significantly lower cardiac output and cardiac index (CI) and a significantly higher mean arterial pressure (MAP)/CI ratio (P<0.05). CI had a cut-off value of 2.6 L/(min·m2), a sensitivity of 79%, a specificity of 83%, and an area under the ROC curve (AUC) of 0.841 in predicting septic shock-related death (P<0.05), and MAP/CI ratio had a cut-off value of 11.4, a sensitivity of 83%, a specificity of 73%, and an AUC of 0.769 (P<0.05). CI had a cut-off value of 2.9 L/(min·m2), a sensitivity of 69%, a specificity of 69%, and an AUC of 0.717 in predicting all-cause death within 28 days (P<0.05). CONCLUSIONS: CI and MAP/CI ratio can be useful for early prediction of septic shock-related death in neonates.

Brief Report: A Case of Tramadol Overdose: Extracorporeal Life Support and Hemoperfusion as Life-Saving Treatment.

We describe the case of a 49-year-old woman with a Tramadol intoxication associated with multiorgan failure. Veno-arterial femoro-femoral extracorporeal life support (VA-ECLS) and hemoperfusion (HP) were used as rescue treatments. The emergency medical service found a woman at home unconscious. Once in the hospital, she was intubated and catecholamines support was immediately started for a severe shock. Brain CT was normal, whereas EEG revealed a metabolic encephalopathy pattern. Toxic levels of Tramadol and Quetiapine were detected. VA-ECLS was implanted due to persistent multiorgan failure, and HP with a charcoal cartridge was set to increase the Tramadol clearance. To quantify the charcoal cartridge's removal efficiency of Tramadol, Tramadol concentration was measured before and after the cartridge and before and after the treatment in the patient's blood. The charcoal cartridge showed good extraction ratio during the treatment and no significant rebound effect. VA-ECLS and HP allowed the patient to be weaned from vasoconstrictors and the resolution of the organ failures. These treatments might be lifesaving in the Tramadol intoxication.

Impella RP in hemodynamically unstable patients with acute pulmonary embolism.

Over the last years, different case reports/studies have demonstrated that in patients with acute pulmonary embolism (PE) and refractory shock mechanical circulatory support (MCS) with Impella RP® (Abiomed, Inc, Danvers, Mass) increases the chances of survival, significantly unloading the right ventricle and improving both the cardiac output and the mean pulmonary artery pressure. We reviewed the medical literature about the use of Impella RP in patients with acute PE and refractory shock using PubMed (MEDLINE), Scopus, Cochrane library, and Google Scholar databases. The final research was conducted in July 2019. The results evidenced that available data are currently scant to definitively assess the real role Impella RP® in patient with acute PE and refractory shock. However, preliminary data seems to be very promising. Further larger studies are needed to confirm the safety and efficacy of MCS in these patients. A multidisciplinary assessment, using the PERT team, must be performed case by case to determine the need of MCS.

Extended Continuous Infusion of Methylene Blue for Refractory Septic Shock.

OBJECTIVE: Highlight the utility of methylene blue (MTB) infusion for extended period for refractory vasoplegia. INTRODUCTION: Hypotension refractory to vasopressor therapy in sepsis is associated with high mortality and limited therapeutic options. Dysregulated nitric oxide (NO) pathway seems to be a major driver, and, therefore, MTB, which inhibits inducible NO synthase activity and decreases cyclic guanosine monophosphate (GMP) accumulation by directly competing with NO by binding to soluble guanylyl cyclase, has been explored. CASE DESCRIPTION: We describe a successful reversal of refractory septic shock with prolonged MTB infusion in a patient supported on multiple vasopressors at the highest clinical doses as well as venovenous extracorporeal membrane oxygenation (VV-ECMO). CONCLUSION AND CLINICAL SIGNIFICANCE: Current report suggests a potential role of MTB infusion in refractory vasoplegia even in advanced vasoplegic shock. HOW TO CITE THIS ARTICLE: Jaiswal A, Kumar M, Silver E. Extended Continuous Infusion of Methylene Blue for Refractory Septic Shock. Indian J Crit Care Med 2020;24(3):206-207.

Multisystem Inflammatory Syndrome in Children: Clinical Features and Management-Intensive Care Experience from a Pediatric Public Hospital in Western India.

BACKGROUND: Multisystem inflammatory syndrome (MIS) associated with severe acute respiratory syndrome coronavirus (SARS-CoV-2) (MIS-C) in children is being increasingly reported across the world. MATERIALS AND METHODS: Children fulfilling the World Health Organization criteria of MIS-C needing pediatric intensive care unit between April 15 and July 26, 2020 were studied. RESULTS: There were 21 patients with median age of 7 years [interquartile range (IQR) 1.9-12.1], of which 11 were females. SARS-CoV-2 real-time polymerase chain reaction positive in 8/21 and/or antibody positive 16/21. Fever was present in all patients, and gastrointestinal symptoms being second most frequent (16/21). One child had aplastic anemia, while the rest had no comorbidities. Nearly all presented with shock (n = 20/21) and 90% needed vasoactive drugs with a median Vasoactive Inotropic Score of 40 (IQR 20-95). Thirteen children needed ventilatory support and one needed peritoneal dialysis. Nine children had left ventricular dysfunction and five had dilatation of coronaries on echocardiography. Inflammatory markers C-reactive protein [98 mg/dL (IQR 89-119)], serum ferritin [710 mg/dL (IQR 422-1,609)], and serum interleukin-6 levels [215 ng/L (IQR 43-527)] were uniformly elevated. Eighteen children received pulse methyl-prednisolone, eleven intravenous immunoglobulins, and four tocilizumab. Eighteen children (86%) were discharged home while three died. CONCLUSION: In our cohort, MIS-C was seen in previously healthy children with fever, gastrointestinal symptoms, and shock. Early and aggressive management of shock and immune modulation with methyl-prednisolone and intravenous immunoglobulin were used. HOW TO CITE THIS ARTICLE: Shobhavat L, Solomon R, Rao S, Bhagat I, Prabhu S, Prabhu S, et al. Multisystem Inflammatory Syndrome in Children: Clinical Features and Management-Intensive Care Experience from a Pediatric Public Hospital in Western India. Indian J Crit Care Med 2020;24(11):1089-1094.

Misdirected Sympathy: The Role of Sympatholysis in Sepsis and Septic Shock.

The spectrum of sepsis and septic shock remains a highly prevalent disease state, carrying a high risk of morbidity and mortality. The sympathetic nervous system (SNS) plays an important role in this initial cascade, enabling the host to respond to invading pathogens; however, prolonged activation can become pathological. The potential for unregulated sympathetic tone to become of detriment in patients with sepsis has fueled interest in the role and impact of sympatholysis, the selective inhibition of sympathetic tone. The cornerstone of septic shock therapy for decades has been the supplementation of catecholamines and thus potential further perpetuation of this sympathetic dysregulation. Although the theory of sympatholysis circulates around cardiovascular effects and stroke volume optimization, the impact of augmenting the SNS may extend well beyond this, including the impacts on the immune system, inflammatory cascade, and even gene transcription. Presently, the most robust clinical evidence involves the use of the cardioselective ß-blocker esmolol in patients with septic shock with persistent tachycardia secondary to catecholamine use. Evidence is isolated only to animal models with α-agonists. Future evidence stands to elucidate the balance of sympathetic and autonomic tone as well as the potential role of redirecting and maximizing sympathetic activity.

Duration of veno-arterial extracorporeal life support (VA ECMO) and outcome: an analysis of the Extracorporeal Life Support Organization (ELSO) registry.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (VA ECMO) is an effective rescue therapy for severe cardiorespiratory failure, but morbidity and mortality are high. We hypothesised that survival decreases with longer VA ECMO treatment. We examined the Extracorporeal Life Support Organization (ELSO) registry for a relationship between VA ECMO duration and in-hospital mortality, and covariates including indication for support. METHODS: All VA runs from the ELSO database from 2002 to 2012 were extracted. Multiple runs and non-VA runs were excluded. Runs were categorized into diagnostic groups. Logistic regression for analysis of the effect of duration on outcome, and multivariate regression for diagnosis and other baseline factors were performed. Non-linear models including piecewise logistic models were fitted. RESULTS: There were 2699 runs analysed over 14,747 days. Logistic regression analysis of the effect of duration on outcome, and multivariate regression analysis of diagnosis and other baseline factors were performed. In-hospital survival was 41.4% (95% CI 39.6-43.3). 75% of patients were supported for less than 1 week and 96% for less than 3 weeks. Median duration (4 days IQR 2.0-6.8) was greater in survivors (4.1 (IQR 2.5-6.7) vs 3.8 (IQR 1.7-7.0) p = 0.002). The final multivariate model demonstrated increasing survival to day 4 (OR 1.53 (95% CI 1.37-1.71) p < 0.001), decreasing from day 4 to 12 (OR 0.86 (95% CI 0.81-0.91), p < 0.001) with no significant change thereafter (OR 0.98 (95% CI 0.94-1.02), p = 0.400). CONCLUSIONS: ECMO for 4 days or less is associated with higher mortality, likely reflecting early treatment failure. Survival is highest when patients are weaned on the fourth day of ECMO but likely decreases into the second week. While this does not suggest weaning at this point will produce better outcomes, it does reflect the likely time course of ECMO as a bridge in severe shock. Patients with some underlying conditions (like myocarditis and heart transplantation) achieve better outcomes despite longer support duration. These findings merit prospective study for the development of prognostic models and weaning strategies.

Angiotensin ii therapy in refractory septic shock: which patient can benefit most? A narrative review.

Patients with septic shock who experience refractory hypotension despite adequate fluid resuscitation and high-dose noradrenaline have high mortality rates. To improve outcomes, evidence-based guidelines recommend starting a second vasopressor, such as vasopressin, if noradrenaline doses exceed 0.5 µg/kg/min. Recently, promising results have been observed in treating refractory hypotension with angiotensin II, which has been shown to increase mean arterial pressure and has been associated with improved outcomes. This narrative review aims to provide an overview of the pathophysiology of the renin-angiotensin system and the role of endogenous angiotensin II in vasodilatory shock with a focus on how angiotensin II treatment impacts clinical outcomes and on identifying the population that may benefit most from its use.

Amiodarone triggered Kounis syndrome complicated by refractory cardiac arrest rescued with VA-ECMO.

Key Clinical Message: An interesting case that shows an infrequent cause of cardiorespiratory arrest such as coronary vasospasm due to intravenous amiodarone induced Kounis syndrome. It highlights the usefulness of circulatory support with ECMO in the scenario of CPR. Abstract: A patient with atrial fibrillation was admitted for an elective electrical cardioversion. He was given an amiodarone bolus that triggered Kounis syndrome with cardiac arrest due to vasospasm requiring emergency coronary angiography with infusion of nitroglycerin. Due to following refractory shock and severe refractory hypoxemia required mechanical circulatory support with ECMO and inhaled nitric oxide with favorable evolution. Allergy to amiodarone was later confirmed.

Effectiveness of the WHO Protocol for the Management of Shock in Children With Severe Acute Malnutrition.

Background The WHO protocol for the management of shock in children with severe acute malnutrition (SAM) is not supported by physiological evidence. In this study, we aimed to assess the effectiveness of the WHO treatment protocol in the management of shock in children with SAM. Methodology This cohort study included children aged 2-60 months with WHO-defined SAM and fulfilling the WHO criteria for identification of shock. The exclusion criteria included severe anemia (hemoglobin <4 g/dL), congenital anomalies, congenital heart defects, and chronic diseases. The WHO treatment protocol for the management of shock was used, and features of resolution of shock were assessed at eight and 24 hours. Oliguria was recorded at eight and 24 hours along with in-hospital mortality. Multiple logistic regression was used to determine predictors of mortality. Results Of 53 children, 40 (75.4%) were discharged and 13 (24.5%) expired. We observed significant resolution of features of shock at 24 hours compared to eight hours (35 (71.4%) vs. 10 (18.8%), p < 0.0001). Further analysis revealed a significant resolution of features of shock (p = 0.03) at 24 hours in both fluid-responsive (24 vs. 10) and fluid-refractory children (11 vs. 27) compared to eight hours. Multivariate analysis revealed that mechanical ventilation was positively related to death (odds ratio (OR) = 85, 95% confidence interval (CI) = 8.49, 860, p < 0.0001), and inotrope scores <20 (OR = 0.053, 95% CI = 0.004, 0.64, p = 0.021) and blood transfusion (OR = 0.025, 95% CI = 0.001, 0.61, p = 0.024) had favorable outcomes. Conclusions The WHO protocol for the management of shock in children with SAM is effective in fluid-responsive shock whereas evidence was inconclusive in fluid-refractory shock.

Refractory Hypotension in an 80-Year-Old Man: A Case Report.

This case report presents the management and diagnosis of an 80-year-old gentleman who presented to the Accident and Emergency Department with refractory hypotension, hypoglycemia, and hyponatremia. Initially diagnosed with sepsis and cellulitis, it was later discovered that the patient was suffering from an Addisonian crisis due to adrenal insufficiency induced by long-term steroid use for rheumatoid arthritis. Prompt administration of intravenous hydrocortisone and fluid resuscitation led to a significant improvement in the patient's condition. This case emphasizes the importance of considering adrenal insufficiency in patients with similar clinical presentations and highlights the critical role of early diagnosis and treatment.

Vasopressor Effect of Indigo Carmine in the Management of Refractory Neurogenic Shock.

Neurogenic shock in patients with spinal cord injuries can be fatal. Catecholamines are commonly used for the management of neurogenic shock; however, the treatment of catecholamine-refractory neurogenic shock remains challenging. A 78-year-old woman with neurogenic shock from cervical cord injury underwent posterior cervical spine decompression and fixation. The patient's blood pressure could not be maintained with catecholamine administration throughout the surgery. Therefore, indigo carmine was administered, and an effective increase in blood pressure was achieved. The postoperative course was uneventful. The findings from this case indicate that indigo carmine may have an effective vasoconstrictive action in patients with neurogenic shock who do not respond to catecholamines.