Early Combination Therapy of Ketamine and Midazolam in Patients with Refractory Status Epilepticus in Hemodynamic Unstable State

The use of anesthetics is inevitable to suppress seizure activity in refractory status epilepticus (RSE). Hypotension, which is a critical side effect observed when treating RSE using a higher dosage of anesthetics that enhance γ-aminobutyric acid (GABA) activity, often requires vasopressor agents. Concomitant treatment with N-methyl-D-aspartate (NMDA) receptor antagonists, such as ketamine, could be effective in prolonged refractory SE, while maintaining stable blood pressure owing to the blockage of catecholamine reuptake in the systemic circulation. We report two cases of patients who had RSE with hemodynamic instability treated promptly with an early combination of ketamine and low-dose midazolam. The combination treatment effectively suppressed epileptic discharge with less hemodynamic side effects; moreover, a low dose of midazolam was required when combined with ketamine therapy. The initial combination of a third-line therapy that blocks NMDA receptors with enhanced GABAergic activity could be useful in RSE. Further studies are necessary in many variable etiologies of SE.

A guide to enteral nutrition in intensive care units: 10 expert tips for the daily practice

The preferential use of the oral/enteral route in critically ill patients over gut rest is uniformly recommended and applied. This article provides practical guidance on enteral nutrition in compliance with recent American and European guidelines. Low-dose enteral nutrition can be safely started within 48 h after admission, even during treatment with small or moderate doses of vasopressor agents. A percutaneous access should be used when enteral nutrition is anticipated for ≥ 4 weeks. Energy delivery should not be calculated to match energy expenditure before day 4–7, and the use of energy-dense formulas can be restricted to cases of inability to tolerate full-volume isocaloric enteral nutrition or to patients who require fluid restriction. Low-dose protein (max 0.8 g/kg/day) can be provided during the early phase of critical illness, while a protein target of > 1.2 g/kg/day could be considered during the rehabilitation phase. The occurrence of refeeding syndrome should be assessed by daily measurement of plasma phosphate, and a phosphate drop of 30% should be managed by reduction of enteral feeding rate and high-dose thiamine. Vomiting and increased gastric residual volume may indicate gastric intolerance, while sudden abdominal pain, distension, gastrointestinal paralysis, or rising abdominal pressure may indicate lower gastrointestinal intolerance.

Vasopressin Loading for Refractory Septic Shock: A Preliminary Analysis of a Case Series

Background: Vasopressin is one of the strong vasopressor agents associated with ischemic events. Responses to the administration of vasopressin differ among patients with septic shock. Although the administration of a high dose of vasopressin needs to be avoided, the effects of bolus loading have not yet been examined. Since the half-life of vasopressin is longer than that of catecholamines, we hypothesized that vasopressin loading may be effective for predicting responses to its continuous administration.Methods: We retrospectively analyzed consecutive cases of septic shock for which vasopressin was introduced with loading under noradrenaline at >0.2 μg/kg/min during the study period. Vasopressin was administered in a 1 U bolus followed by its continuous administration at 1 U/h. The proportion of patients with a negative catecholamine index (CAI) change 6 h after the introduction of vasopressin was set as the primary outcome. We defined non-responders for exploration as those with a mean arterial pressure change <18 mmHg 1 min after vasopressin loading, among whom none had a change in CAI <0.Results: Twenty-one consecutive cases were examined in the present study, and included 14 responders and 7 non-responders. The primary outcome accounted for 71.4% of responders and 0% of non-responders, with a significant difference (p = 0.0039). Median CAI changes 2, 4, and 6 h after the administration of vasopressin were 0, −5, and −10 in responders and +20, +10, and +10 in non-responders, respectively. CAI was not reduced in any non-responder. Outcomes including mortality were not significantly different between responders and non-responders. Digital ischemia (1/21) and mesenteric ischemia (1/21) were observed.Conclusions: Vasopressin loading may predict responses to its continuous administration in septic shock patients. Further investigations involving a safety analysis are needed.

Treatment With Vasopressor Agents for Cardiovascular Shock Patients With Poor Renal Function; Results From the Japanese Circulation Society Cardiovascular Shock Registry

According to the guidelines for cardiogenic shock, norepinephrine is associated with fewer arrhythmias than dopamine and may be the better first-line vasopressor agent. This study aimed to evaluate the utility of norepinephrine vs. dopamine as first-line vasopressor agent for cardiovascular shock depending on the presence and severity of renal dysfunction at hospitalization. This was a secondary analysis of the prospective, multicenter Japanese Circulation Society Cardiovascular Shock Registry (JCS Shock Registry) conducted between 2012 and 2014, which included patients with shock complicating emergency cardiovascular disease at hospital arrival. The analysis included 240 adult patients treated with norepinephrine alone (n = 98) or dopamine alone (n = 142) as the first-line vasopressor agent. Primary endpoint was mortality at 30 days after hospital arrival. The two groups had similar baseline characteristics, including estimated glomerular filtration rate (eGFR), and similar 30-day mortality rates. The analysis of the relationship between 30-day mortality rate after hospital arrival and vasopressor agent used in patients categorized according to the eGFR-based chronic kidney disease classification revealed that norepinephrine as the first-line vasopressor agent might be associated with better prognosis of cardiovascular shock in patients with mildly compromised renal function at admission (0.0 vs. 22.6%; P = 0.010) and that dopamine as the first-line vasopressor agent might be beneficial for cardiovascular shock in patients with severely compromised renal function [odds ratio; 0.22 (95% confidence interval 0.05–0.88; P = 0.032)]. Choice of first-line vasopressor agent should be based on renal function at hospital arrival for patients in cardiovascular shock.Clinical Trial Registration:http://www.umin.ac.jp/ctr/, Unique identifier: 000008441.

Effect of treatment applied in sepsis on intensive care unit and hospital stay: how effective are albumin/steroid/vasopressor agents?

Background The incidence and prevalence of sepsis have increased in recent years and it is the most common cause of intensive care admission. The aim of this study was to determine the effects of albumin, steroid, and vasopressor agents and other possible factors on the duration of intensive care unit and hospital stay in sepsis patients. Open access data set obtained from Tohoku Sepsis Registry database was used. Four hundred sixty-two patients admitted to intensive care unit with the diagnosis of sepsis were divided into four groups according to their intensive care unit (≤ 5 or > 5 days) and hospital length of stay (≤ 24 or > 24 days). Demographic data, vital signs, laboratory values, mechanical ventilation requirement, and treatment protocols such as albumin, steroid, and vasopressor agent use were used in the evaluation of the groups. Results The use of albumin (odds ratio [OR] = 3.76 [95% confidence interval (CI), 2.16–6.56]; p < 0.001), steroids (OR = 2.85 [95% CI, 1.67–4.86]; p < 0.001), and vasopressor agents (OR = 3.56 [95% CI, 2.42–5.24]; p < 0.001) were associated with an increasing risk of prolonged intensive care unit length of stay. Also, it was found that the use of albumin (OR = 3.43 [95% CI, 2.00–5.89]; p < 0.001), steroids (OR = 2.81 [95% CI, 1.66–4.78]; p < 0.001), and vasopressor agents (OR = 4.47 [95% CI, 3.02–6.62]; p < 0.001) were associated with an increasing risk of prolonged hospital length of stay. In addition, prognostic scoring systems, body temperature, mean arterial pressure, pH, PaO2/FiO2 ratio, and mechanical ventilation requirement in the first 24 h were also found to be associated with length of stay in intensive care unit and hospital. There was a significant relationship between platelet count, creatinine, Na, lactic acid, and time between diagnosis of sepsis and source control and intensive care unit length of stay, and between hematocrit and C-reactive protein and hospital length of stay. Conclusions The use of albumin, steroid, and vasopressor agents has been found to be significantly correlated with both intensive care unit and hospital length of stay. Further studies are needed to determine in what order or at what dosage these agents will be administered in sepsis treatment.

Hypersensitivity Reactions and Anaphylaxis

Allergic reactions vary in intensity from mild rash or allergic rhinitis to devastating anaphylactic shock. Anaphylaxis, often underrecognized and undertreated, can be a life-threatening syndrome leading to multiorgan dysfunction. This review covers the etiology, pathophysiology, and treatment of severe allergic reactions and anaphylaxis. It is precipitated by exposure to particular allergens—commonly food, medications, insect stings, and environmental exposures—in a previously sensitized individual. Symptoms develop from an IgE-mediated immune response leading to degranulation of mast cells and basophils and the release of preformed mediators, lipid-derived metabolites, and inflammatory cytokines. First-line treatment for anaphylaxis involves epinephrine. Secondary treatments are antihistamines and corticosteroids. Further treatments for patients refractory to standard therapies involve vasopressor agents, nebulized albuterol, and glucagon. Frequency and duration of biphasic reactions are variable, limiting the development of consensus guidelines for monitoring of anaphylactic reactions. Figures show the immune activity and inflammatory pathways in allergic responses, mast cell degranulation, and a depiction of common organs involved and corresponding clinical manifestations. Tables list the criteria for diagnosis of anaphylaxis, classification of hypersensitivity reactions, common clinical manifestations, and etiology and mediators of anaphylaxis. This review contains 4 highly rendered figures, 11 tables, and 43 references. Key words: allergy, anaphylaxis, antihistamine, corticosteroid, epinephrine, mast cells

Feasibility and Safety of Peripheral Intravenous Administration of Vasopressor Agents in Resource-limited Settings

BackgroundVasopressors are conventionally administered through a central venous catheter (CVC) and not through a peripheral venous catheter (PVC) since the latter is believed to be associated with increased risk of extravasation. Placement of a CVC requires suitably trained personnel to be on hand, and in resource-limited settings, this requirement may delay placement. Because of this and in cases where suitably trained personnel are not immediately available, some clinicians may be prompted to utilise a PVC for infusing vasopressors. The objective of this study is to assess the feasibility and safety of vasopressors administered through a PVC.Materials and methodsPatients who received vasopressors through a PVC for more than one hour were included in a single centre, consecutive patient observational study. Patients with a CVC at the time of initiation of vasopressors were excluded. Data regarding the size, location of PVCs, dose, duration and number of vasopressors infused were recorded. The decision to place CVC was left to the discretion of the treating physician. Extravasation incidents, severity and management of such events were recorded.ResultsOne hundred twenty-two patients age 55(4) years [mean (SD)] were included in the study. The commonest PVC was of 18G calibre (57%), and the most common site of placement was the external jugular vein (36.5%). Noradrenaline was the most common vasopressor used at a dose of 10.6 (7) mcg/min [mean (SD)] and the median duration of nine hours (IQR: 6-14). CVC was placed most commonly due to an increasing dose of vasopressors after 4.5(4) hours [mean (SD)]. Grade 2 Extravasation injury occurred in one patient after prolonged infusion of fifty-two hours, through a small calibre (20G) PVC, which was managed conservatively without any sequelae.ConclusionVasopressors infused through a PVC of 18G or larger calibre into the external jugular, or a forearm vein is feasible and safe. Clinicians need to balance the safety of peripheral vasopressor infusion with the additional costs and complications associated with CVC in resource-limited settings.

Pediatric Palliative Care During End of Life: A Privilege of a Few in a Tertiary Referral Hospital From Colombia

Background: We aim to describe the access to palliative care (PC) in hospitalized children during end-of-life care and compare the circumstances surrounding the deaths of hospitalized children as a basis for implementing a pediatric PC program at our institution. Methods: We performed a retrospective chart review of deceased pediatric patients at a tertiary referral hospital in Colombia. The study group was selected by randomly drawing a sample of 100 observations from the 737 deceased children from 2013 to 2016. A 1:1 propensity score (PS) matching was performed to compare the characteristics and outcomes between PC and non-PC treated patients. Results: We included 87 patients. After PS matching, we found that patients under the care of non-PC physicians were more likely to die in the pediatric intensive care unit (non-PC: 6/10 vs PC: 1/10; P = .02), to be on vasopressor agents and mechanical ventilation (non-PC: 7/10 vs PC: 1/10; P = .02), and to receive cardiopulmonary resuscitation at the end of life (non-PC: 5/10 vs PC: 0/10; P = .03). In contrast, a significantly higher proportion of patients under the care of the pediatric PC team died with comfort measures (non-PC: 2/10 vs 8/10; P = .02) and nonescalation of care in physician orders (non-PC: 5/10 vs PC: 10/10; 0.03). Conclusion: In this study, only 10 of 87 patients were treated by the pediatric PC team at the end of life. The latter finding is concerning and is a call to action to improve access to pediatric PC at our institution.