Concept: Intensive care medicine
To the Editor: Zika virus (ZIKV) is currently spreading widely, while its clinical spectrum remains a matter of investigation. Evidence of a relationship between ZIKV infection and cerebral birth abnormalities(1),(2) is growing.(3) An increased incidence of some peripheral nervous syndromes among adults was reported during outbreaks in French Polynesia(4),(5) and Brazil,(1),(2) but no formal link with ZIKV infection was shown. We describe a case of central nervous system infection with ZIKV that was associated with meningoencephalitis in an adult. An 81-year-old man was admitted to the intensive care unit (ICU) 10 days after he had been on . . .
Background Whether hydrocortisone reduces mortality among patients with septic shock is unclear. Methods We randomly assigned patients with septic shock who were undergoing mechanical ventilation to receive hydrocortisone (at a dose of 200 mg per day) or placebo for 7 days or until death or discharge from the intensive care unit (ICU), whichever came first. The primary outcome was death from any cause at 90 days. Results From March 2013 through April 2017, a total of 3800 patients underwent randomization. Status with respect to the primary outcome was ascertained in 3658 patients (1832 of whom had been assigned to the hydrocortisone group and 1826 to the placebo group). At 90 days, 511 patients (27.9%) in the hydrocortisone group and 526 (28.8%) in the placebo group had died (odds ratio, 0.95; 95% confidence interval [CI], 0.82 to 1.10; P=0.50). The effect of the trial regimen was similar in six prespecified subgroups. Patients who had been assigned to receive hydrocortisone had faster resolution of shock than those assigned to the placebo group (median duration, 3 days [interquartile range, 2 to 5] vs. 4 days [interquartile range, 2 to 9]; hazard ratio, 1.32; 95% CI, 1.23 to 1.41; P<0.001). Patients in the hydrocortisone group had a shorter duration of the initial episode of mechanical ventilation than those in the placebo group (median, 6 days [interquartile range, 3 to 18] vs. 7 days [interquartile range, 3 to 24]; hazard ratio, 1.13; 95% CI, 1.05 to 1.22; P<0.001), but taking into account episodes of recurrence of ventilation, there were no significant differences in the number of days alive and free from mechanical ventilation. Fewer patients in the hydrocortisone group than in the placebo group received a blood transfusion (37.0% vs. 41.7%; odds ratio, 0.82; 95% CI, 0.72 to 0.94; P=0.004). There were no significant between-group differences with respect to mortality at 28 days, the rate of recurrence of shock, the number of days alive and out of the ICU, the number of days alive and out of the hospital, the recurrence of mechanical ventilation, the rate of renal-replacement therapy, and the incidence of new-onset bacteremia or fungemia. Conclusions Among patients with septic shock undergoing mechanical ventilation, a continuous infusion of hydrocortisone did not result in lower 90-day mortality than placebo. (Funded by the National Health and Medical Research Council of Australia and others; ADRENAL ClinicalTrials.gov number, NCT01448109 .).
Background Acetaminophen is a common therapy for fever in patients in the intensive care unit (ICU) who have probable infection, but its effects are unknown. Methods We randomly assigned 700 ICU patients with fever (body temperature, ≥38°C) and known or suspected infection to receive either 1 g of intravenous acetaminophen or placebo every 6 hours until ICU discharge, resolution of fever, cessation of antimicrobial therapy, or death. The primary outcome was ICU-free days (days alive and free from the need for intensive care) from randomization to day 28. Results The number of ICU-free days to day 28 did not differ significantly between the acetaminophen group and the placebo group: 23 days (interquartile range, 13 to 25) among patients assigned to acetaminophen and 22 days (interquartile range, 12 to 25) among patients assigned to placebo (Hodges-Lehmann estimate of absolute difference, 0 days; 96.2% confidence interval [CI], 0 to 1; P=0.07). A total of 55 of 345 patients in the acetaminophen group (15.9%) and 57 of 344 patients in the placebo group (16.6%) had died by day 90 (relative risk, 0.96; 95% CI, 0.66 to 1.39; P=0.84). Conclusions Early administration of acetaminophen to treat fever due to probable infection did not affect the number of ICU-free days. (Funded by the Health Research Council of New Zealand and others; HEAT Australian New Zealand Clinical Trials Registry number, ACTRN12612000513819 .).
Sepsis, severe sepsis, and septic shock represent increasingly severe systemic inflammatory responses to infection. Sepsis is common in the aging population, and it disproportionately affects patients with cancer and underlying immunosuppression. In its most severe form, sepsis causes multiple organ dysfunction that can produce a state of chronic critical illness characterized by severe immune dysfunction and catabolism. Much has been learnt about the pathogenesis of sepsis at the molecular, cell, and intact organ level. Despite uncertainties in hemodynamic management and several treatments that have failed in clinical trials, investigational therapies increasingly target sepsis induced organ and immune dysfunction. Outcomes in sepsis have greatly improved overall, probably because of an enhanced focus on early diagnosis and fluid resuscitation, the rapid delivery of effective antibiotics, and other improvements in supportive care for critically ill patients. These improvements include lung protective ventilation, more judicious use of blood products, and strategies to reduce nosocomial infections.
Background Intracranial-pressure monitoring is considered the standard of care for severe traumatic brain injury and is used frequently, but the efficacy of treatment based on monitoring in improving the outcome has not been rigorously assessed. Methods We conducted a multicenter, controlled trial in which 324 patients 13 years of age or older who had severe traumatic brain injury and were being treated in intensive care units (ICUs) in Bolivia or Ecuador were randomly assigned to one of two specific protocols: guidelines-based management in which a protocol for monitoring intraparenchymal intracranial pressure was used (pressure-monitoring group) or a protocol in which treatment was based on imaging and clinical examination (imaging-clinical examination group). The primary outcome was a composite of survival time, impaired consciousness, and functional status at 3 months and 6 months and neuropsychological status at 6 months; neuropsychological status was assessed by an examiner who was unaware of protocol assignment. This composite measure was based on performance across 21 measures of functional and cognitive status and calculated as a percentile (with 0 indicating the worst performance, and 100 the best performance). Results There was no significant between-group difference in the primary outcome, a composite measure based on percentile performance across 21 measures of functional and cognitive status (score, 56 in the pressure-monitoring group vs. 53 in the imaging-clinical examination group; P=0.49). Six-month mortality was 39% in the pressure-monitoring group and 41% in the imaging-clinical examination group (P=0.60). The median length of stay in the ICU was similar in the two groups (12 days in the pressure-monitoring group and 9 days in the imaging-clinical examination group; P=0.25), although the number of days of brain-specific treatments (e.g., administration of hyperosmolar fluids and the use of hyperventilation) in the ICU was higher in the imaging-clinical examination group than in the pressure-monitoring group (4.8 vs. 3.4, P=0.002). The distribution of serious adverse events was similar in the two groups. Conclusions For patients with severe traumatic brain injury, care focused on maintaining monitored intracranial pressure at 20 mm Hg or less was not shown to be superior to care based on imaging and clinical examination. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01068522 .).
Background Previous trials suggesting that high-frequency oscillatory ventilation (HFOV) reduced mortality among adults with the acute respiratory distress syndrome (ARDS) were limited by the use of outdated comparator ventilation strategies and small sample sizes. Methods In a multicenter, randomized, controlled trial conducted at 39 intensive care units in five countries, we randomly assigned adults with new-onset, moderate-to-severe ARDS to HFOV targeting lung recruitment or to a control ventilation strategy targeting lung recruitment with the use of low tidal volumes and high positive end-expiratory pressure. The primary outcome was the rate of in-hospital death from any cause. Results On the recommendation of the data monitoring committee, we stopped the trial after 548 of a planned 1200 patients had undergone randomization. The two study groups were well matched at baseline. The HFOV group underwent HFOV for a median of 3 days (interquartile range, 2 to 8); in addition, 34 of 273 patients (12%) in the control group received HFOV for refractory hypoxemia. In-hospital mortality was 47% in the HFOV group, as compared with 35% in the control group (relative risk of death with HFOV, 1.33; 95% confidence interval, 1.09 to 1.64; P=0.005). This finding was independent of baseline abnormalities in oxygenation or respiratory compliance. Patients in the HFOV group received higher doses of midazolam than did patients in the control group (199 mg per day [interquartile range, 100 to 382] vs. 141 mg per day [interquartile range, 68 to 240], P<0.001), and more patients in the HFOV group than in the control group received neuromuscular blockers (83% vs. 68%, P<0.001). In addition, more patients in the HFOV group received vasoactive drugs (91% vs. 84%, P=0.01) and received them for a longer period than did patients in the control group (5 days vs. 3 days, P=0.01). Conclusions In adults with moderate-to-severe ARDS, early application of HFOV, as compared with a ventilation strategy of low tidal volume and high positive end-expiratory pressure, does not reduce, and may increase, in-hospital mortality. (Funded by the Canadian Institutes of Health Research; Current Controlled Trials numbers, ISRCTN42992782 and ISRCTN87124254 , and ClinicalTrials.gov numbers, NCT00474656 and NCT01506401 .).
The patient had not yet coded but was spiraling downward, prompting a request for a bed in the intensive care unit (ICU). But the ICU had no available beds. Hours passed before the decision was made that another patient could safely be “bumped” out of the unit to accommodate our patient. After the transfer, in the empty room strewn with unused bottles, procedure kits, and hospital gowns, there was a moment of peaceful quiet but weariness. The team was exhausted from worrying that the patient would code before being transferred to the ICU, from running a makeshift ICU on a . . .
Sepsis is a common cause of death in the intensive care unit with mortality up to 70% when accompanied by multiple organ dysfunction. Rapid diagnosis and the institution of appropriate antibiotic therapy and pressor support are therefore critical for survival. MicroRNAs are small non-coding RNAs that play an important role in the regulation of numerous cellular processes, including inflammation and immunity.
Various hydroxyethyl starch (HES) preparations have been used for decades to augment blood volume. There has been concern recently regarding possible adverse outcomes when using HES in the intensive care setting, especially in patients with septic shock. However, the pharmacokinetic and pharmacodynamic properties of HES preparations depend on their chemical composition and source material. Thus, different clinical conditions could result in differing effectiveness and safety for these preparations. Consequently, we assessed the safety of tetrastarches when used during surgery, using a formal search, that yielded 59 primary full publications of studies that met a priori inclusion criteria and randomly allocated 4529 patients with 2139 patients treated with tetrastarch compared with 2390 patients treated with a comparator. There were no indications that the use of tetrastarches during surgery induces adverse renal effects as assessed by change or absolute concentrations of serum creatinine or need for renal replacement therapy (39 trials, 3389 patients), increased blood loss (38 trials, 3280 patients), allogeneic erythrocyte transfusion (20 trials, 2151 patients; odds ratio for HES transfusion 0.73 [95% confidence interval = 0.61-0.87], P = 0.0005), or increased mortality (odds ratio for HES mortality = 0.51 [0.24-1.05], P = 0.079).
BACKGROUND: The mortality rate of patients complicated with sepsis-associated organ failure remains high in spite of intensive care treatment. The purpose of this study was to define the duration of systemic inflammatory response syndrome (SIRS) before organ failure (DSOF) and determine the value of DSOF as a prognostic factor in septic patients. METHODS: This retrospective cohort study was conducted in an 11-bed medical and surgical intensive care unit (ICU) in a university hospital. The primary endpoint was in-hospital mortality of the septic patients. RESULTS: One hundred ten septic patients with organ failure and/or shock were enrolled in this study. The in-hospital mortality rate was 36.9%. The median DSOF was 28.5 h. As a metric variable, DSOF was a statistically significant prognostic factor according to univariate analysis (survivor: 74.7 +/- 9.6 h, non-survivor: 58.8 +/- 16.5 h, p = 0.015). On the basis of the ROC curve, we defined an optimal cutoff of 24 h, with which we divided the patients as follows: group 1 (n = 50) comprised patients with a DSOF <=24 h, and group 2 (n = 60) contained patients with a DSOF >24 h. There were statistically significant differences in the in-hospital mortality rate between the two groups (52.0% vs. 25.0%, p = 0.004). Furthermore, by multivariate analysis, DSOF <=24 h (odds ratio: 5.89, 95% confidence interval: 1.46-23.8, p = 0.013) was a significant independent prognostic factor. CONCLUSION: DSOF may be a useful prognostic factor for severe sepsis.