Advantages and disadvantages of etomidate use for intubation of patients with sepsis

Etomidate is a potent imidazole hypnotic used widely in single doses in the rapid sequence intubation of critically ill patients with sepsis due to its presumed hemodynamic safety, fast onset, and short duration of action. However, the literature is conflicting regarding the hemodynamic advantages of etomidate over other induction agents, and its safety in this population is a matter of strong debate in the critical care community as the drug is associated with suppression of adrenal steroidogenesis, which can last up to 72 hours after a single dose, primarily through potent inhibition of the 11β-hydroxylase enzyme. However, the clinical impact of this adrenal suppressive effect is not certain. The use of continuous-infusion etomidate in critically ill patients was abandoned more than 20 years ago due to reports of increased mortality. Nevertheless, mortality data of single-dose etomidate are still controversial, with no strong evidence of benefit over other agents and a tendency toward harm (keeping in mind the limitations of the available literature). Proponents of single-dose etomidate use in patients with sepsis suggest that the increased mortality associated with etomidate is merely a reflection of the patients' severity of illness and not related to the drug itself, whereas others believe that the drug causes true harm and increases mortality in this population. In view of the lack of a clear clinical advantage of etomidate over other agents used in rapid sequence intubation, it would be prudent to favor other agents until further conclusive evidence of etomidate safety is available in critically ill patients with sepsis.     

In vivo mesna and amifostine do not prevent chloroacetaldehyde nephrotoxicity in vitro

Chloroacetaldehyde (CAA) is the putative metabolite responsible for ifosfamide-induced nephrotoxicity. Whereas evidence suggests that sodium 2-mercaptoethanesulfonate (mesna) and amifostine protect renal cells against CAA toxicity in vitro, their efficacy in clinical studies is controversial. To better understand the discrepancy between in vivo and in vitro results, we combined the in vivo intraperitoneal administration of either saline or mesna (100 mg/kg) or amifostine (200 mg/kg) in rats and the in vitro study of CAA toxicity to both proximal tubules and precision-cut renal cortical slices. The measured renal cortical concentrations of mesna and amifostine were 0.6±0.1 μmol/g and 1.2±0.2 μmol/g, respectively; these drugs did not cause renal toxicity. Despite this, none of the adverse effects of 0.5 mM CAA was prevented by the previous in vivo administration of mesna or amifostine. Toxicity of 0.5 mM CAA to rat proximal tubules was shown by the fall of cellular adenosine triphosphate (ATP), total glutathione and coenzyme A + acetyl-coenzyme A levels and by the altered metabolic viability of renal cells. Long-term exposure of cortical slices to CAA concentrations ≥30 μM caused severe cell toxicity (i.e. decrease in cellular ATP, total glutathione, and coenzyme A + acetyl-coenzyme A levels), which was not prevented by the in vivo administration of mesna or amifostine.     

Pro/Con debate: Should 24/7 in-house intensivist coverage be implemented?

You are appointed director of a new large multi-discipline intensive care unit in an academic center. The hospital is affiliated with a medical school and as such there will be an adequate number of medical students, residents, and fellows (specializing in critical care) rotating through the unit. The unit will be a 'closed' (intensivist-led) model. In setting up the call schedule for the intensivists, you need to decide whether the mandate will be for the intensivists to provide 24/7 in-house coverage as opposed to off-hour coverage from home. You wonder about the sustainability of each model.     

The safety of percutaneous tracheostomy in patients with coagulopathy or thrombocytopenia

The safety and complications of percutaneous tracheostomy (PT) without bronchoscopic guidance in a group of ICU patients with thrombocytopenia platelet count of < or = 60.000/mm3) or coagulopathy (INR > or = 1.5 or systemic heparinization), was studied. During the study period (May 2004-June 2005), 190 percutaneous tracheostomies were performed. Of these there were 11 (6%) patients with prolonged INR, 7 (4%) patients with thrombocytopenia and 14 (7%) patients on systemic heparin. There was no evidence of bleeding in patients with prolonged INR. A minor bleeding developed in only one patient with thrombocytopenia, and in two patients receiving systemic heparin. The PT was aborted for one patient with thrombocytopenia and slight increase of INR (1.3) due to major bleeding in spite of transfusion of both platelets and FFP. Our data suggest the incidence of bleeding is low in patients with coagulopathy and or thrombocytopenia-undergoing PT without bronchoscopic guidance.     

Histopathology of Middle East respiratory syndrome coronovirus (MERS‐CoV) infection – clinicopathological and ultrastructural study

Aims

The pathogenesis, viral localization and histopathological features of Middle East respiratory syndrome – coronavirus (MERS‐CoV) in humans are not described sufficiently. The aims of this study were to explore and define the spectrum of histological and ultrastructural pathological changes affecting various organs in a patient with MERS‐CoV infection and represent a base of MERS‐CoV histopathology.

Methods and results

We analysed the post‐mortem histopathological findings and investigated localisation of viral particles in the pulmonary and extrapulmonary tissue by transmission electron microscopic examination in a 33‐year‐old male patient of T cell lymphoma, who acquired MERS‐CoV infection. Tissue needle biopsies were obtained from brain, heart, lung, liver, kidney and skeletal muscle. All samples were collected within 45 min from death to reduce tissue decomposition and artefact. Histopathological examination showed necrotising pneumonia, pulmonary diffuse alveolar damage, acute kidney injury, portal and lobular hepatitis and myositis with muscle atrophic changes. The brain and heart were histologically unremarkable. Ultrastructurally, viral particles were localised in the pneumocytes, pulmonary macrophages, renal proximal tubular epithelial cells and macrophages infiltrating the skeletal muscles.

Conclusion

The results highlight the pulmonary and extrapulmonary pathological changes of MERS‐CoV infection and provide the first evidence of the viral presence in human renal tissue, which suggests tissue trophism for MERS‐CoV in kidney.

     

Non-pulmonary infections but not specific pathogens are associated with increased risk of AKI in septic shock

Introduction

Little is known regarding the relationship between the anatomic infection site and etiologic pathogen with the occurrence of acute kidney injury (AKI) in severe infections. We set out to determine the association between the site of infection, type of pathogen in septic shock and occurrence of AKI.

Methods

Using a large, international multicenter database that included data from 28 academic and community hospitals, we retrospectively analyzed adult (age >18 years) cases of septic shock occurring between January 1996 and December 2008. Early acute kidney injury (AKI) was classified by the RIFLE criteria at or within 24 h of shock diagnosis. Multivariate logistic regression was used to determine the association between the infection site/microbial pathogen and occurrence of AKI. Analyses were adjusted for demographics, illness severity, comorbidities and intensive care unit interventions (partial adjustment) ± site of infection and microbial pathogen (full adjustment).

Results

After exclusions, 4,493 cases from potentially eligible patients in the database were included in the analytic cohort of whom 3,298 (73.4 %) experienced AKI. Patients with AKI were older (p < 0.0001), had a higher mean Acute Physiology and Chronic Health Evaluation score (p < 0.0001), and had greater laboratory and hemodynamic abnormalities. The most common site of infection among septic shock patients with AKI was the lung (34.5 %), followed by gastrointestinal (GI) (26.2 %) and urinary (15.3 %) sources. Likewise, the most common infecting organism among septic shock patients with AKI was E. coli (23.9 %) followed by S. aureus (GI) (16.1 %) and other enterobacteriaceae (15.7 %). There was a large degree of variability in the occurrence of AKI based on the site of infection and the pathogen in unadjusted analysis (p < 0.0001), which persisted with partial (excluding infection site and microbial pathogen grouping) adjustment (p < 0.0001). Fully adjusted multivariate analysis showed significant variations in AKI only in relation to the anatomic source of infection, with non-pulmonary infections having higher risk than pulmonary infections. The pathogen group/pathogen had no significant independent impact on AKI.

Conclusion

This study demonstrates that the presence of septic AKI varies significantly based on the site of infection but not the type of causative organism.     

Clinical characteristics,sepsis interventions and outcomes in the obese patients with septic shock: an international multicenter cohort study

Introduction

Data are sparse as to whether obesity influences the risk of death in critically ill patients with septic shock. We sought to examine the possible impact of obesity, as assessed by body mass index (BMI), on hospital mortality in septic shock patients.

Methods

We performed a nested cohort study within a retrospective database of patients with septic shock conducted in 28 medical centers in Canada, United States and Saudi Arabia between 1996 and 2008. Patients were classified according to the World Health Organization criteria for BMI. Multivariate logistic regression analysis was performed to evaluate the association between obesity and hospital mortality.

Results

Of the 8,670 patients with septic shock, 2,882 (33.2%) had height and weight data recorded at ICU admission and constituted the study group. Obese patients were more likely to have skin and soft tissue infections and less likely to have pneumonia with predominantly Gram-positive microorganisms. Crystalloid and colloid resuscitation fluids in the first six hours were given at significantly lower volumes per kg in the obese and very obese patients compared to underweight and normal weight patients (for crystalloids: 55.0 ± 40.1 ml/kg for underweight, 43.2 ± 33.4 for normal BMI, 37.1 ± 30.8 for obese and 27.7 ± 22.0 for very obese). Antimicrobial doses per kg were also different among BMI groups. Crude analysis showed that obese and very obese patients had lower hospital mortality compared to normal weight patients (odds ratio (OR) 0.80, 95% confidence interval (CI) 0.66 to 0.97 for obese and OR 0.61, 95% CI 0.44 to 0.85 for very obese patients). After adjusting for baseline characteristics and sepsis interventions, the association became non-significant (OR 0.80, 95% CI 0.62 to 1.02 for obese and OR 0.69, 95% CI 0.45 to 1.04 for very obese).

Conclusions

The obesity paradox (lower mortality in the obese) documented in other populations is also observed in septic shock. This may be related in part to differences in patient characteristics. However, the true paradox may lie in the variations in the sepsis interventions, such as the administration of resuscitation fluids and antimicrobial therapy. Considering the obesity epidemic and its impact on critical care, further studies are warranted to examine whether a weight-based approach to common therapeutic interventions in septic shock influences outcome.     

Emergency room to the intensive care unit in Hajj. The chain of life

Hajj, which brings more than 2 million Muslims together, represents a special challenge for healthcare services especially the intensive care unit. The main goal for healthcare providers is to provide the best service to the largest number of patients with the available resources. The purpose of this article is to outline the admission criteria from the emergency room to the intensive care and to review some of the unique features of providing these services during the Hajj season.