Nonalcoholic Wernicke’s Encephalopathy Associated with Unintentional Weight Loss, Cholecystectomy, and Intractable Vomiting: The Role of Dual Thiamine and Corticosteroid Therapy

A 23-year-old male with one month of intractable vomiting, subsequent cholecystitis status post cholecystectomy, and overall 40-pound weight loss over the last few months presented with altered mental status and seizures. MRI showed signal abnormalities involving the hypothalamus, periaqueductal gray matter, 4th ventricle, and bilateral thalami, indicative of Wernicke's encephalopathy. The patient was started on empiric IV thiamine and methylprednisolone; thiamine levels were subsequently found to be low. Infectious disease workup was negative. Within a few days of this therapy, the patient's neurological status steadily improved with increased responsiveness and communication. Repeat MRI 7 days after admission showed significant resolution of the signal abnormalities. Over the next several weeks the patient became fully conversational, cognitively intact, and increasingly ambulatory. Nonalcoholic Wernicke's encephalopathy is rare; there have been reports relating it separately to vomiting and invasive surgery. In this case report, we associate it with both recurrent vomiting and minimally invasive cholecystectomy. We also discuss combinatorial therapy of thiamine and corticosteroids, which is poorly defined in the literature. Though there is no consensus-based optimal treatment of Wernicke's encephalopathy, this adds to the discussion of using dual therapy and supports that the use of empiric corticosteroids does not harm the patient

Nitric Oxide Scavenging by Red Blood Cell Microparticles and Cell-Free Hemoglobin as a Mechanism for the Red Cell Storage Lesion

Background— Intravascular red cell hemolysis impairs nitric oxide (NO)–redox homeostasis, producing endothelial dysfunction, platelet activation, and vasculopathy. Red blood cell storage under standard conditions results in reduced integrity of the erythrocyte membrane, with formation of exocytic microvesicles or microparticles and hemolysis, which we hypothesized could impair vascular function and contribute to the putative storage lesion of banked blood. Methods and Results— We now find that storage of human red blood cells under standard blood banking conditions results in the accumulation of cell-free and microparticle-encapsulated hemoglobin, which, despite 39 days of storage, remains in the reduced ferrous oxyhemoglobin redox state and stoichiometrically reacts with and scavenges the vasodilator NO. Using stopped-flow spectroscopy and laser-triggered NO release from a caged NO compound, we found that both free hemoglobin and microparticles react with NO about 1000 times faster than with intact erythrocytes. In complementary in vivo studies, we show that hemoglobin, even at concentrations below 10 μmol/L (in heme), produces potent vasoconstriction when infused into the rat circulation, whereas controlled infusions of methemoglobin and cyanomethemoglobin, which do not consume NO, have substantially reduced vasoconstrictor effects. Infusion of the plasma from stored human red blood cell units into the rat circulation produces significant vasoconstriction related to the magnitude of storage-related hemolysis. Conclusions— The results of these studies suggest new mechanisms for endothelial injury and impaired vascular function associated with the most fundamental of storage lesions, hemolysis. </jats:sec

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Hypertensive Emergencies (DRAFT)

Hypertensive emergencies may be encountered by rapid response teams (RRTs). Various forms of acute organ dysfunction separate hypertensive urgency from hypertensive emergency. These include acute heart failure, acute coronary syndrome, acute aortic dissection, ischemic stroke, hemorrhagic stroke, hypertensive encephalopathy, sympathetic crisis, postoperative hypertension, and hypertensive emergencies in pregnancy. RRTs must be able to rapidly assess the patient’s condition, initiate treatment, and triage the patient to the appropriate level of care. This chapter summarizes the initial evaluation and triage of the patient as well as the blood pressure reduction goals in the acute period for the various conditions associated with hypertensive emergencies, discussing suggested drugs with the dosages, and looking at common pitfalls.</p

Nonalcoholic Wernicke’s Encephalopathy Associated with Unintentional Weight Loss, Cholecystectomy, and Intractable Vomiting: The Role of Dual Thiamine and Corticosteroid Therapy

A 23-year-old male with one month of intractable vomiting, subsequent cholecystitis status post cholecystectomy, and overall 40-pound weight loss over the last few months presented with altered mental status and seizures. MRI showed signal abnormalities involving the hypothalamus, periaqueductal gray matter, 4th ventricle, and bilateral thalami, indicative of Wernicke’s encephalopathy. The patient was started on empiric IV thiamine and methylprednisolone; thiamine levels were subsequently found to be low. Infectious disease workup was negative. Within a few days of this therapy, the patient’s neurological status steadily improved with increased responsiveness and communication. Repeat MRI 7 days after admission showed significant resolution of the signal abnormalities. Over the next several weeks the patient became fully conversational, cognitively intact, and increasingly ambulatory. Nonalcoholic Wernicke’s encephalopathy is rare; there have been reports relating it separately to vomiting and invasive surgery. In this case report, we associate it with both recurrent vomiting and minimally invasive cholecystectomy. We also discuss combinatorial therapy of thiamine and corticosteroids, which is poorly defined in the literature. Though there is no consensus-based optimal treatment of Wernicke’s encephalopathy, this adds to the discussion of using dual therapy and supports that the use of empiric corticosteroids does not harm the patient

Improving delivery of low tidal volume ventilation in 10 ICUs

Low tidal volume ventilation (LTVV) is standard of care for mechanically ventilated patients with acute respiratory distress syndrome and has been shown to improve outcomes in the general mechanically ventilated population. Despite these improved outcomes, in clinical practice the LTVV standard of care is often not met. We aimed to increase compliance with LTVV in mechanically ventilated patients in 10 intensive care units at 3 hospitals within the University of Pittsburgh School of Medicine Department of Critical Care Medicine. Four Plan-Do-Study-Act (PDSA) cycles were implemented to improve compliance with LTVV. Initial compliance rates of 40.6%–60.1% improved to 91%–96% by the end of the fourth PDSA cycle. The most impactful step in the intervention was providing education and giving responsibility of selecting the tidal volume to the respiratory therapist. The overall intervention resulted in improved compliance with LTVV that has been sustained for multiple years after our active PDSA cycles.</jats:p