A Review of Fluid Bolus in Critically Ill Patients After Initial Volume Expansion: Bayesian Probability Analysis and Case Studies.

Introduction Fluid resuscitation is a crucial intervention for the management of critically ill patients. However, after initial volume expansion, the advantages of fluid bolus administration remain controversial. Our aim was to investigate the probabilistic reasoning against fluid bolus administration in critically ill patients after initial volume expansion. We then applied this reasoning to two hypothetical case studies that evaluated the benefits and risks associated with a fluid bolus for each patient. Methods We analyzed data from 12 previously published studies, totaling 334 patients, on fluid responsiveness in critically ill patients. Owing to differences in these studies, we used a Monte Carlo simulation based on their parameters to improve our Bayesian prior, generate strong estimates, and address uncertainty. Using the established Bayesian prior for volume responsiveness, we scrutinized two hypothetical case studies employing Bayesian mathematical notation to assess the pre-test probability, posterior probability, and likelihood ratios in patients with septic shock. Results The Monte Carlo simulation yielded a mean response rate of 0.54 (SD = 0.026), suggesting that only approximately 54% of patients were responsive to fluid bolus administration. These results had an effective sample size of 17,204 and an R-hat value of 1, demonstrating the reliability of our results. In our Bayesian case studies, we demonstrate the low probabilities of volume and VO2 responsiveness over time using common bedside testing. Conclusion Our analysis shows that the pretest and posttest probabilities for volume responsiveness following initial fluid resuscitation are low. Additional bedside testing should be pursued before administering additional volume. This approach emphasizes the importance of evidence-based decision-making in the management of critically ill patients to optimize patient outcomes and minimize potential risks.

Oral Midodrine as an Adjunct in Rapid Weaning of Intravenous Vasopressor Support in Spinal Cord Injury.

Background Majority of acute cervical spinal cord injury end up requiring long-term stay in intensive care unit (ICU). During the initial few days after spinal cord injury, most patients are hemodynamically unstable requiring intravenous vasopressors. However, many studies have noted that long-term intravenous vasopressors remain the main reason for prolongation of ICU stay. In this series, we report the effect of using oral midodrine in reducing the amount and duration of intravenous vasopressors in patients with acute cervical spinal cord injury. Materials and Methods Five adult patients with cervical spinal cord injury after initial evaluation and surgical stabilization are assessed for the need for intravenous vasopressors. If patients continue to need intravenous vasopressors for more than 24 hours, they were started on oral midodrine. Its effect on weaning of intravenous vasopressors was assessed. Results Patients with systemic and intracranial injury were excluded from the study. Midodrine helped in weaning of intravenous vasopressors in the first 24 to 48 hours and helped in complete weaning of intravenous vasopressors. The rate of reduction was between 0.5 and 2.0 µg/min. Conclusion Oral midodrine does have an effect in reduction of intravenous vasopressors for patients needing prolonged support after cervical spine injury. The real extent of this effect needs to be studied with collaboration of multiple centers dealing with spinal injuries. The approach seems to be a viable alternative to rapidly wean intravenous vasopressors and reduce duration of ICU stay.

Refractory hypotension secondary to chronic treatment with high doses of quetiapine.

Quetiapine is an atypical antipsychotic used in the treatment of depressive, schizophrenic, or bipolar disorders. It acts on dopamine D1 and D2, histamine, and 5HT1A and 5HT2 receptors. However, it also acts as an antagonist for α1 receptors causing cardiovascular side effects, including hypotension. We present the case of a patient chronically medicated with Quetiapine who developed hypotension refractory to vasoconstrictors and intraoperative fluid therapy. Noradrenalin has a strong α1 effect with lower affinity for ß2 receptors unlike adrenalin. This translates into peripheral vasoconstriction and an improved clinical picture. Therefore, it should be considered the vasoactive drug of choice in patients on high doses of Quetiapine.

Hipotensión refractaria secundaria a tratamiento crónico con altas dosis de quetiapina / Refractory hypotension secondary to chronic treatment with high doses of quetiapine

La quetiapina es un antipsicótico atípico que se usa en el tratamiento del trastorno depresivo, esquizofrénico o bipolar. Su acción reside en su acción sobre los receptores de la dopamina D1 y D2, histamina y serotonina 5HT1A y 5HT2. Sin embargo, también tiene antagonismo para los receptores α1, provocando efectos secundarios cardiovasculares, entre ellos la hipotensión. Presentamos el caso de un paciente medicado crónicamente con quetiapina que presentó hipotensión refractaria a vasoconstrictores y fluidoterapia intraoperatoria. La noradrenalina tiene un fuerte efecto α1 con una menor afinidad para los receptores β2 a diferencia de la adrenalina. Esto se traduce en una vasoconstricción periférica y la resultante mejoría del cuadro clínico. Por lo tanto, se debe considerar el fármaco vasoactivo de elección en la hipotensión refractaria en pacientes que tomen altas dosis de quetiapina.(AU)

Quetiapine is an atypical antipsychotic used in the treatment of depressive, schizophrenic, or bipolar disorders. It acts on dopamine D1 and D2, histamine, and 5HT1A and 5HT2 receptors. However, it also acts as an antagonist for α1 receptors causing cardiovascular side effects, including hypotension. We present the case of a patient chronically medicated with quetiapine who developed hypotension refractory to vasoconstrictors and intraoperative fluid therapy. Noradrenalin has a strong α1 effect with lower affinity for β2 receptors unlike adrenalin. This translates into peripheral vasoconstriction and an improved clinical picture. Therefore, it should be considered the vasoactive drug of choice in patients on high doses of quetiapine.(AU)

ACE-Inhibitor or ARB-Induced Refractory Hypotension Treated With Vasopressin in Patients Undergoing General Anesthesia for Dentistry: Two Case Reports.

Two case reports present the use of vasopressin for treating refractory hypotension associated with continued angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) therapy prior to general anesthesia for oral surgery. Both patients were treated in an ambulatory dental surgery clinic and took either their ACEI or ARB medication for hypertension within 24 hours prior to undergoing an intubated general anesthetic. Persistent profound hypotension was encountered intraoperatively that was refractory to treatment with traditional methods. However, the ACEI- or ARB-induced refractory hypotension was successfully managed with the administration of vasopressin.

A Rare Case of Intravenous Amiodarone Toxicity.

Amiodarone is a highly effective treatment for life-threatening supraventricular and ventricular arrhythmias, namely in the setting of acutely decompensated heart failure. However, it could be associated with several serious adverse effects both in long-term oral therapy and in short-term use of intravenous (IV) preparation, including shock and liver injury. We report an unusual case of life-threatening refractory hypotension associated with acute hepatitis and renal failure a few hours after initiation of IV amiodarone. A 70-year-old man was admitted to the emergency department (ED) with dyspnea, chest discomfort, and a non-productive cough. Physical examination and complementary diagnostic tests helped diagnose acutely decompensated heart failure due to atrial fibrillation (AF) with a rapid ventricular response, and IV amiodarone was started. A few hours after initiating this drug, the patient developed hypotension with the need for inotropic therapy, acute elevation of amino transaminases, and renal failure. Renal function and liver transaminases returned to baseline after discontinuing amiodarone. A Roussel Uclaf Causality Assessment Method (RUCAM) score of 5 identifies our patient`s acute hepatitis as a possible adverse drug reaction. Refractory hypotension and liver injury with acute hepatitis after a short-term IV amiodarone therapy are extremely rare with few previously reported cases. Therefore, it is very important to perform continuous hemodynamic monitoring of the patient and liver function monitorization during short-term IV administration of this drug because these complications can be potentially fatal. A high index of suspicion is the key to functional organic recovery.

A pilot, feasibility, randomised controlled trial of midodrine as adjunctive vasopressor for low-dose vasopressor-dependent hypotension in intensive care patients: The MAVERIC study.

PURPOSE: To assess the feasibility and physiological efficacy of adjunctive midodrine in patients with vasopressor-dependent hypotension. MATERIALS AND METHODS: This was a pilot, open label, randomised controlled trial. Patients were enrolled from two tertiary intensive care units on low dose intravenous vasopressor therapy for more than 24 h. We randomly assigned patients to receive either adjunctive midodrine (10 mg every 8 h) or usual care. The primary efficacy outcome was time to cessation of intravenous vasopressor therapy. Secondary outcomes included protocol compliance, ICU and hospital length of stay. RESULTS: We screened 381 patients over 22-months and enrolled 62 (32 in midodrine group, 30 in usual care group). Median time to cessation of vasopressor infusion was 16.5 h for midodrine vs 19 h for usual care (p = 0.22). Time in ICU (50 [25.50, 74.00] hours for midodrine v 59 [38.50, 93.25] hours for usual care, p = 0.14) and hospital length of stay (9 days vs. 7.5 days, p = 0.92) were similar. Protocol compliance was 96.9%. One patient ceased midodrine early due to symptomatic bradycardia. CONCLUSIONS: Adjunctive midodrine therapy was feasible with acceptable compliance, duration of therapy, and safety profile. However, at the chosen dose, there was no evidence of physiological or clinical efficacy.

Hyperinsulinemia/euglycemia and intravenous lipid emulsion therapy for the management of severe amlodipine toxicosis in a cat.

Calcium-channel blockers (CCBs) are widely used in people and animals. Overdose can result in cardiovascular collapse and death. Hyperinsulinemia/euglycemia therapy (HIET) and intralipid therapy (ILT) are reported treatment options in people. This is the first report describing HIET and ILT as treatments for amlodipine toxicosis in a cat.

Prolonged Washout Period for Avoiding Azilsartan-Induced Refractory Hypotension During General Anesthesia for a Patient With Renal Impairment.

Angiotensin receptor blockers (ARBs) are widely used to treat hypertension, but severe refractory hypotension during general anesthesia is a well-known complication associated with the continuation of ARBs during the perioperative period. It has therefore been recommended that ARBs be withheld for 24 hours before induction of general anesthesia. However, impaired renal function affects the pharmacokinetics of each ARB differently. The half-life of azilsartan is prolonged in accordance with the degree of renal impairment. Herein, we describe a patient with chronic kidney disease grade 3B who experienced severe refractory hypotension after induction of general anesthesia requiring administration of dopamine following inadequate responses to ephedrine and phenylephrine despite a 24-hour azilsartan washout period. When the same patient underwent general anesthesia for a subsequent surgery, azilsartan was withheld for 48 hours before induction, resulting in mild intraoperative hypotension that responded adequately to phenylephrine. Severe refractory hypotension during general anesthesia cannot always be avoided by holding azilsartan for 24 hours in patients with significant renal impairment. Therefore, a longer washout period may be preferable for patients regularly taking azilsartan who also have concurrent substantial renal impairment.

Echocardiography-Guided Resuscitation in Noncardiac Surgery.

Sustained hypotension impairs perfusion, causing permanent organ damage, neurologic deficit, and cardiac arrest. Emerging evidence suggests that noncardiac anesthesia providers can use echocardiography to manage refractory hypotension. Echocardiographic findings may reveal the underlying pathology of hemodynamic compromise and can guide the selection of appropriate resuscitative measures. The current evidence was reviewed to evaluate echocardiography's impact on the cause, diagnosis, and resuscitation management of refractory hypotension during noncardiac surgery. An extensive literature search yielded 3 prospective interventional studies and 7 observational studies, which were graded and ranked by quality, consistency, and strength of recommendations according to the United States Preventive Services Task Force evidence evaluation grading system. Echocardiographic imaging was useful in all phases of perioperative care, from the preoperative clinic through the postanesthesia care unit. Focused echocardiographic examination of the heart and great vessels contributed critical diagnostic data that expedited management decisions. As a primary cardiovascular monitor, transesophageal echocardiography guided both fluid resuscitation and pharmacologic therapy. During intraoperative cardiac arrest, transesophageal echocardiography enhanced diagnostic insight and directly guided targeted, lifesaving treatment. Noninvasive transthoracic echocardiography offered providers several clinical advantages. The published literature validates echocardiography's utility in the diagnosis and treatment of patients experiencing intraoperative refractory hypotension due to hemodynamic compromise.

Refractory hypotension in post-operative setting with raised intracranial pressure: insula at play?

Raised Intra-Cranial Pressure causes hypertension. We report a 75 years old lady with large Middle Cerebral Artery bifurcation aneurysm that was operated on. Post-operatively she had a progressive hypotension that was refractory to inotropes and became life threatening. There was subgaleal, extradural and subdural collection of Cerebro-Spinal Fluid. Drainage of this collection led to immediate complete recovery from hypotension, normalization of tachycardia and improvement in sensorium within 4 hours. Raised Intra-Cranial Pressure can manifest with hypotension and tachycardia if the right insula has been exposed. Removal of the irritant can lead to rapid and complete recovery.

Case Report: Refractory Hypotension of GABA B Receptor Autoimmune Encephalitis.

Introduction: With the development of antibody detection technology, Gamma-Aminobutyric Acid (GABA) B receptor encephalitis is a known autoimmune disease. This paper describes a patient with refractory hypotension who suffered GABA B receptor autoimmune encephalitis. Case Report: We describe a 63-year-old man with GABA B receptor autoimmune encephalitis who had hypotension on day 17 of the disease onset. Despite two rounds of immunoglobulin administration, high-dose intravenous steroid injections and immunosuppressive therapy on day 35 of hospitalization, psychiatric symptoms and seizures were significantly improved; however, the patient's blood pressure remained low. Conclusion: This case study and literature review investigated the impairment of autonomic nerve function and its subsequent management in patients with GABA B receptor autoimmune encephalitis.

Refractory Hypotension During General Anesthesia Despite Withholding Telmisartan.

Angiotensin receptor blockers (ARBs) are commonly used to treat hypertension. However, similar to angiotensin-converting enzyme inhibitors, ARBs can also cause refractory hypotension during general anesthesia. Therefore, it has been recommended that ARBs be withheld for 24 hours prior to the induction of anesthesia. This is a case report of refractory hypotension requiring the administration of potent vasopressors after the induction of general anesthesia despite withholding telmisartan for 24 hours. In the same patient undergoing a subsequent general anesthetic, telmisartan was withheld for 5 days before induction, leading to mild intraoperative hypotension that responded adequately to phenylephrine. The primary cause of refractory hypotension during the first general anesthetic was suspected to be an insufficient telmisartan washout period. Telmisartan's half-life of 24 hours is notably the longest of all ARBs in current use. This case report demonstrates that refractory hypotension during general anesthesia cannot always be avoided by withholding telmisartan for 24 hours before the induction of anesthesia. Therefore, a washout period greater than 24 hours is preferable for patients taking telmisartan.

Late-Onset Circulatory Collapse and Risk of Cerebral Palsy in Extremely Preterm Infants.

OBJECTIVE: To investigate whether the development of postnatal, late-onset refractory hypotension, referred to as late-onset circulatory collapse, was associated with an increased risk of developing cerebral palsy (CP) at 3 years of age in extremely preterm infants. METHODS: In this historical cohort study, infants who were born at 22-27 weeks of gestation from 2008 to 2012 in the Neonatal Research Network of Japan were eligible. The study sample consisted of 3474 infants (45.6% of 7613 potentially eligible infants) who were evaluated at 36-42 months of age. Late-onset circulatory collapse was defined as a clinical diagnosis of late-onset circulatory collapse requiring treatment with corticosteroids. We compared the neurodevelopmental outcomes between infants with and without late-onset circulatory collapse. RESULTS: Late-onset circulatory collapse was diagnosed in 666 of the infants studied. Infants with late-onset circulatory collapse had a higher incidence of CP than those without late-onset circulatory collapse (18.0% vs 9.8%; P < .01). In multivariable logistic analysis, late-onset circulatory collapse was independently associated with CP (aOR, 1.52; 95% CI, 1.13-2.04) and developmental quotient score of <50 (OR, 1.83; 95% CI, 1.23-2.72). CONCLUSIONS: Late-onset circulatory collapse may be a relatively common event occurring in extremely preterm infants and an independent risk factor for CP at 3 years of age.

Case report on intravenous octreotide for the treatment of intraoperative vasoplegia following thymoma resection.

Octreotide is a somatostatin analog known for its role in the treatment of acute variceal bleeding, enterocutaneous fistula and carcinoid syndrome. The reduction of portal pressure from splanchnic vasoconstriction has been attributed to the inhibition of nitric oxide synthesis, guanylate cyclase and release of glucagon. Octreotide has many therapeutic applications as a result of the ubiquitous nature of somatostatin receptors throughout the body. The effects of octreotide on vascular tone make it potentially useful in the treatment of intraoperative vasoplegia, hypotension with low systemic vascular resistance with preserved cardiac output that is refractory to adrenergic agonists. We present a case in which a patient undergoing thymoma resection developed vasoplegia that was effectively treated with octreotide. We believe that this case illustrates the need for further investigation on the potential efficacy of octreotide as an adjunct for the treatment of vasoplegia and other forms of shock.

Refractory Hypotension Caused by Prazosin Overdose Combined With Acetaminophen and Naproxen Toxicity: A Case Report and Review of the Literature.

BACKGROUND: Pediatric exposure to prazosin is unusual because it is most commonly indicated for the treatment of hypertension. Prazosin's increase in popularity as a treatment for posttraumatic stress disorder makes it important for emergency physicians to be aware of how to manage potential toxic ingestion because of prazosin overdose. CASE REPORT: A 16-year-old, 76-kg female presented after ingesting 110 mg of prazosin, 209.3 g of acetaminophen, and 55 g of naproxen. She was admitted to the pediatric intensive care unit for rapidly deteriorating hypotension (lowest blood pressure 47/19 mm Hg) refractory to aggressive fluid resuscitation and infusions of epinephrine and norepinephrine each at 0.5 mcg/kg/min. Stabilization of blood pressure was eventually achieved, and associated with use of a vasopressin infusion of 0.004 units/kg/min. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Because of the increasing exposure of children to prazosin, clinicians should be aware of the pharmacology behind alpha-1 antagonist overdose and consider treatment options, such as vasopressin, when hypotension is resistant to standard fluid and catecholamine therapy.

Dihydroxyacetone as a definitive treatment for aluminium phosphide poisoning in rats.

Aluminium phosphide (AlP), a very toxic pesticide also known as the rice tablet, releases phosphine gas upon contact with water, moisture, or gastric acid. Its mortality rate in humans is 70-100 % due to cardiogenic shock and refractory hypotension. Dihydroxyacetone (DHA) is a simple ketonic carbohydrate, mainly used for sunless skin tanning. It also plays a beneficial role in the treatment of hypotension and cardiogenic shock by restoring blood volume and cellular respiration. The aim of this study was to investigate the its effect on the haemodynamics and electrocardiogram (ECG) in male rats poisoned with AlP. The animals were divided into the following groups: control (received 1 mL corn oil, orally), AlP (received 15 mg kg-1 AlP solved in corn oil, orally), AlP plus DHA (treated with 50 mg kg-1 of DHA 30 min after receiving AlP), and AlP plus N-acetyl cysteine (NAC) (treated with 200 mg kg-1 of NAC 30 min after receiving AlP). The animals were then anaesthetised and ECG, blood pressure, and heart rate were recorded for 120 min. Treatment with AlP alone and in combination with NAC was associated with progressive hypotension, tachycardia, and ECG disturbances in rats, resulting in 100 % mortality 3 h after poisoning. However, DHA achieved 100 % survival in the poisoned rats and prevented AlP-induced ECG and haemodynamic abnormalities. The main mechanism of DHA in the treatment of AlP poisoning is unclear, but the findings suggest the promising therapeutic potential of DHA against AlP poisoning.

Methylene Blue as an Adjunct to Treat Vasoplegia in Patients Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass: A Literature Review.

The term vasoplegia describes hypotension refractory to vasopressor therapy, a common finding related to cardiac surgery requiring cardiopulmonary bypass. High doses of vasoactive agents are associated with adverse effects such as peripheral and mesenteric ischemia. Databases were systematically searched for literature on methylene blue as an adjunct therapy to treat vasoplegia. Fifteen articles were selected. The quality of the studies was evaluated using the US Preventive Services Task Force (USPSTF) grading tool, and a chart was created to present the components of each study. Preoperative, intraoperative, and postoperative administration of methylene blue has been shown to increase systemic vascular resistance and mean arterial pressure, with the period after surgery being the most common time for use of this therapy. Decreased vasopressor requirements have also been consistently demonstrated after methylene blue administration. This catecholamine-sparing effect prevents vasopressor-related injury. Its favorable safety profile as well as hemodynamic effects have made methylene blue a valuable adjunct in the setting of vasoplegia. Methylene blue is an effective treatment of refractory hypotension related to cardiac surgery requiring cardiopulmonary bypass. Larger, randomized controlled trials are needed to strengthen the state of the evidence and to define specific doses.

A polymorphism in the glucocorticoid receptor gene is associated with refractory hypotension in premature infants.

BACKGROUND: Glucocorticoids play an important role in endocrine control. The association of glucocorticoid receptor (GR) gene polymorphisms with altered sensitivity to glucocorticoid therapy has been reported in adults. However, there are few such reports in infants. The present study analyzed the prevalence of four GR polymorphisms in preterm infants born before 30 weeks of gestation and determined the associations between these polymorphisms and clinical outcomes in the infants. METHODS: Totally, 41 preterm infants born at two hospitals in Fukushima were retrospectively screened for the presence of four GR gene polymorphisms, using a TaqMan single-nucleotide polymorphism genotyping assay. The effect of GR gene polymorphisms on clinical outcomes during hospitalization was evaluated. The following primary clinical outcomes were assessed: refractory hypotension in the acute phase and/or severe bronchopulmonary dysplasia, maximum dopamine and dobutamine doses administered, and total hydrocortisone dose administered in the first 48 h of life. Multivariate analysis with logistic regression was used to assess the association between clinical factors and refractory hypotension. RESULTS: Of the four GR polymorphisms, only the BclI polymorphism was detected. The genotype distribution was as follows: C/C, 33; C/G, 8; and G/G, 0 infants. Significant differences were observed between the C/C and C/G genotypes with respect to the following variables: refractory hypotension (6% vs. 50%), dopamine dose [3.0 (2.0-4.0) vs. 4.8 (4.0-7.5) µg/kg/min], dobutamine dose [2.4 (0.0-3.6) vs. 4.0 (0-10.0) µg/kg/min], and total hydrocortisone dose administered in the first 48 h of life [2.0 (0-10.0) vs. 6.0 (0-12.0) mg/kg]. Multivariate analysis showed that the BclI genotype (C/C) was significantly less associated with refractory hypotension in the acute phase (odds ratio, 0.008; 95% confidence interval, 0.000-0.371; p = 0.013). CONCLUSION: The incidence of refractory hypotension in infants with the C/C genotype was initially expected to be higher than that in infants with the C/G genotype. However, the results of this study were rather different from what we originally expected. The suppressive effect of antenatal steroid use on the HPA axis of the preterm infants with the BclI variant may be associated with refractory hypotension in the acute phase.

Cortisol precursors in neonates with vasopressor-resistant hypotension in relationship to demographic characteristics.

OBJECTIVE: To correlate between cortisol precursors in neonates with vasopressor resistant hypotension and demographic characteristics. METHODS: We investigated 48 neonates with vasopressor-resistant hypotension. Gestation at birth ranged from 34 to 42 weeks and postnatal age from 4 to 14 days. Cortisol and precursor steroids were measured soon after the onset of volume expansion and inotropes for treatment of shock. Their concentrations were determined using liquid chromatography/mass spectrometry. RESULTS: In neonates with vasopressor-resistant hypotension, the serum levels of cortisol were within normal nonstress range. There was a strong negative linear association between postnatal age and dehydroepiandrosterone level (r = -0.50, p < .01), which decreased with neonatal age. In addition, there was a significant positive association between gestational age at birth and 17-hydroxy-pregnenolone (r = 0.33, p = .02). No further significant associations were evident between the neonatal weight, duration of gestation or gender and of the levels of cortisol or the other steroids (p > .05). The cause of therapy-resistant hypotension did not appear to influence the steroid levels. CONCLUSIONS: Cortisol stress response is absent in these severely ill late preterm and term infants. This may be due to inhibition of the distal pathway of cortisol synthesis.