A Pilot Feasibility Randomized Controlled Trial of Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit: The Lessening Organ Dysfunction with Vitamin C-India (LOVIT-India) Trial.

Background: The burden of sepsis is high in India and is associated with substantial morbidity and mortality. Vitamin C, an endogenous antioxidant, may improve patient outcomes. Methods: This was a parallel-group pilot feasibility randomized controlled trial conducted at 2 intensive care units in India. Adult patients (≥18 years) with proven or suspected infection as the main diagnosis and needing a continuous intravenous vasopressor infusion were randomized to intravenous vitamin C (50 mg/kg every 6 hours for a maximum of 16 doses) or matching placebo. Primary outcomes were related to protocol adherence and feasibility (enrollment per month). The key secondary outcome was the composite of mortality or persistent organ dysfunction (POD) at day 28 after randomization. Results: 60 patients were screened, 51 were eligible, 32 were randomized, and 30 were included in the analysis (randomized/eligible ratio: 0.63). The overall rate of enrollment was 1.5 patients per month. The median (IQR) age was 63.5 (51.0, 70.0) and 70.0% of the patients were male. In both arms, all patients received ≥90% of scheduled doses of the study drug. No patient received open-label vitamin C and there were no deviations from the glucose monitoring protocol. The composite outcome of mortality or POD at day 28 occurred in 56.3% (9/16) in the vitamin C arm as compared to 42.9% (6/14) in the placebo arm [RR: 1.31 (95% CI: 0.62, 2.76), p = 0.47]. Conclusion: In this pilot feasibility randomized controlled trial of vitamin C for adult patients with sepsis, protocol adherence was excellent and feasibility endpoints were met. Trial registration: CTRI/2020/03/024371. How to cite this article: Vijayaraghavan BKT, Venkataraman R, Ramanathan Y, Margabandhu S, Jayakumar D, Ramachandran P, et al. A Pilot Feasibility Randomized Controlled Trial of Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit: The Lessening Organ Dysfunction with Vitamin C-India (LOVIT-India) Trial. Indian J Crit Care Med 2023;27(12):910-916.

Critical care delivery across health care systems in low-income and low-middle-income country settings: A systematic review.

Background: Prior research has demonstrated that low- and low-middle-income countries (LLMICs) bear a higher burden of critical illness and have a higher rate of mortality from critical illness than high-income countries (HICs). There is a pressing need for improved critical care delivery in LLMICs to reduce this inequity. This systematic review aimed to characterise the range of critical care interventions and services delivered within LLMIC health care systems as reported in the literature. Methods: A search strategy using terms related to critical care in LLMICs was implemented in multiple databases. We included English language articles with human subjects describing at least one critical care intervention or service in an LLMIC setting published between 1 January 2008 and 1 January 2020. Results: A total of 1620 studies met the inclusion criteria. Among the included studies, 45% of studies reported on pediatric patients, 43% on adults, 23% on infants, 8.9% on geriatric patients and 4.2% on maternal patients. Most of the care described (94%) was delivered in-hospital, with the remainder (6.2%) taking place in out-of-hospital care settings. Overall, 49% of critical care described was delivered outside of a designated intensive care unit. Specialist physicians delivered critical care in 60% of the included studies. Additional critical care was delivered by general physicians (40%), as well as specialist physician trainees (22%), pharmacists (16%), advanced nursing or midlevel practitioners (8.9%), ambulance providers (3.3%) and respiratory therapists (3.1%). Conclusions: This review represents a comprehensive synthesis of critical care delivery in LLMIC settings. Approximately 50% of critical care interventions and services were delivered outside of a designated intensive care unit. Specialist physicians were the most common health care professionals involved in care delivery in the included studies, however generalist physicians were commonly reported to provide critical care interventions and services. This study additionally characterised the quality of the published evidence guiding critical care practice in LLMICs, demonstrating a paucity of interventional and cost-effectiveness studies. Future research is needed to understand better how to optimise critical care interventions, services, care delivery and costs in these settings. Registration: PROSPERO CRD42019146802.

Effect of video camera monitoring feedback on hand hygiene compliance in neonatal intensive care unit, an interventional study.

BACKGROUND: The purpose of this study was to determine whether use of a video camera surveillance system for hand hygiene (HH) monitoring, video-based education, and feedback could improve the HH compliance in a neonatal intensive care unit (NICU). METHODS AND MATERIALS: This was an interventional before-after trial conducted in a level-III NICU between July 2019 and June 2020. HH compliance was measured using randomly selected video-camera footage in the baseline, intervention, and maintenance periods. After the baseline, an intervention consisting of feedback and education with video scenarios was implemented. The primary outcome was change in HH compliance. The compliance rates were analyzed as an interrupted time series (ITS) with a segmented regression model adjusted for autocorrelation for each study period. RESULTS: We identified a total of 8335 HH indications. There were non significant increases in the total compliance rate (9.0%, 95% CI -2% to 20%) at the time of intervention and in the compliance rate after intervention (0.26%, 95% CI -0.31% to 0.84%) per day. The hand hygiene compliance before patient contact significantly increased (19.8%, 95% CI, 4.8%-34.8%). Incorrect glove use improved non-significantly with the intervention (-3.4%, 95% CI -13.4% to 6.7%). CONCLUSION: In this study of HH monitoring using video-camera footage combined with an intervention including feedback and education, there were inconsistent improvements in HH compliance. However, these improvements were not sustained in the long term. Frequent feedback and education may be required to sustain high compliance.

Lessening Organ Dysfunction With Vitamin C (LOVIT) Trial: Statistical Analysis Plan.

BACKGROUND: The LOVIT (Lessening Organ Dysfunction with Vitamin C) trial is a blinded multicenter randomized clinical trial comparing high-dose intravenous vitamin C to placebo in patients admitted to the intensive care unit with proven or suspected infection as the main diagnosis and receiving a vasopressor. OBJECTIVE: We aim to describe a prespecified statistical analysis plan (SAP) for the LOVIT trial prior to unblinding and locking of the trial database. METHODS: The SAP was designed by the LOVIT principal investigators and statisticians, and approved by the steering committee and coinvestigators. The SAP defines the primary and secondary outcomes, and describes the planned primary, secondary, and subgroup analyses. RESULTS: The SAP includes a draft participant flow diagram, tables, and planned figures. The primary outcome is a composite of mortality and persistent organ dysfunction (receipt of mechanical ventilation, vasopressors, or new renal replacement therapy) at 28 days, where day 1 is the day of randomization. All analyses will use a frequentist statistical framework. The analysis of the primary outcome will estimate the risk ratio and 95% CI in a generalized linear mixed model with binomial distribution and log link, with site as a random effect. We will perform a secondary analysis adjusting for prespecified baseline clinical variables. Subgroup analyses will include age, sex, frailty, severity of illness, Sepsis-3 definition of septic shock, baseline ascorbic acid level, and COVID-19 status. CONCLUSIONS: We have developed an SAP for the LOVIT trial and will adhere to it in the analysis phase. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/36261.

Administration of Parenteral Vitamin C in Patients With Severe Infection: Protocol for a Systematic Review and Meta-analysis.

BACKGROUND: Severe infections are characterized by inflammation and oxidative damage. Ascorbic acid (vitamin C) administration may attenuate oxidative damage and, in turn, reduce vascular endothelial injury in pulmonary and systemic vasculature. OBJECTIVE: We aim to describe a protocol for a living systematic review that will evaluate the effectiveness and safety of parenteral vitamin C administration in adults with severe infections, including those with COVID-19. METHODS: We searched Ovid MEDLINE, Embase, CINAHL, the Centers for Disease Control and Prevention COVID-19 database, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to March 30, 2021, for randomized controlled trials evaluating parenteral vitamin C versus no parenteral vitamin C in hospitalized adults with severe infection. Eligible studies will include at least 1 arm involving any dose of parenteral vitamin C alone or in combination with other cointerventions and at least 1 arm not involving parenteral vitamin C. The primary outcomes of interest will include in-hospital, 30-day, and 90-day mortality. Title and abstract screening, full-text screening, data extraction, and risk of bias evaluation via a modified Risk of Bias 2.0 tool will be conducted independently and in pairs. We will perform random effects modeling for meta-analyses, in which study weights will be generated by using the inverse variance method. We will assess certainty in effect estimates by using the Grading of Recommendations Assessment, Development and Evaluation methodology. Meta-analyses will be updated iteratively as new trial evidence becomes available. RESULTS: Among the 1386 citations identified as of March 30, 2021, a total of 17 eligible randomized controlled trials have been identified as of September 2021. We are in the process of updating the search strategy and associated data analyses. CONCLUSIONS: The results will be of importance to critical care physicians and hospitalists who manage severe infection and COVID-19 in daily practice, and they may directly inform international clinical guidance. Although our systematic review will incorporate the most recent trial evidence, ongoing trials may change our confidence in the estimates of effects, thereby necessitating iterative updates in the form of a living review. TRIAL REGISTRATION: PROSPERO CRD42020209187; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=209187. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/33989.

Critical care service delivery across healthcare systems in low-income and low-middle-income countries: protocol for a systematic review.

INTRODUCTION: Critical care in low-income and low-middle income countries (LLMICs) is an underdeveloped component of the healthcare system. Given the increasing growth in demand for critical care services in LLMICs, understanding the current capacity to provide critical care is imperative to inform policy on service expansion. Thus, our aim is to describe the provision of critical care in LLMICs with respect to patients, providers, location of care and services and interventions delivered. METHODS AND ANALYSIS: We will search PubMed/MEDLINE, Web of Science and EMBASE for full-text original research articles available in English describing critical care services that specify the location of service delivery and describe patients and interventions. We will restrict our review to populations from LLMICs (using 2016 World Bank classifications) and published from 1 January 2008 to 1 January 2020. Two-reviewer agreement will be required for both title/abstract and full text review stages, and rate of agreement will be calculated for each stage. We will extract data regarding the location of critical care service delivery, the training of the healthcare professionals providing services, and the illnesses treated according to classification by the WHO Universal Health Coverage Compendium. ETHICS AND DISSEMINATION: Reviewed and exempted by the Stanford University Office for Human Subjects Research and IRB on 20 May 2020. The results of this review will be disseminated through scholarly publication and presentation at regional and international conferences. This review is designed to inform broader WHO, International Federation for Emergency Medicine and partner efforts to strengthen critical care globally. PROSPERO REGISTRATION NUMBER: CRD42019146802.

Correction: Hill, A.; et al. Effects of Vitamin C on Organ Function in Cardiac Surgery Patients: A Systematic Review and Meta-Analysis. Nutrients 2019, 11, 2103.

The authors thank the readers for pointing out the issues [...].

Pharmacological interventions for the treatment of delirium in critically ill adults.

BACKGROUND: Although delirium is typically an acute reversible cognitive impairment, its presence is associated with devastating impact on both short-term and long-term outcomes for critically ill patients. Advances in our understanding of the negative impact of delirium on patient outcomes have prompted trials evaluating multiple pharmacological interventions. However, considerable uncertainty surrounds the relative benefits and safety of available pharmacological interventions for this population. OBJECTIVES: Primary objective1. To assess the effects of pharmacological interventions for treatment of delirium on duration of delirium in critically ill adults with confirmed or documented high risk of deliriumSecondary objectivesTo assess the following:1. effects of pharmacological interventions on delirium-free and coma-free days; days with coma; delirium relapse; duration of mechanical ventilation; intensive care unit (ICU) and hospital length of stay; mortality; and long-term outcomes (e.g. cognitive; discharge disposition; health-related quality of life); and2. the safety of such treatments for critically ill adult patients. SEARCH METHODS: We searched the following databases from their inception date to 21 March 2019: Ovid MEDLINE®, Ovid MEDLINE® In-Process & Other Non-Indexed Citations, Embase Classic+Embase, and PsycINFO using the Ovid platform. We also searched the Cochrane Library on Wiley, the International Prospective Register of Systematic Reviews (PROSPERO) (http://www.crd.york.ac.uk/PROSPERO/), the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science. We performed a grey literature search of relevant databases and websites using the resources listed in Grey Matters developed by the Canadian Agency for Drugs and Technologies in Health (CADTH). We also searched trial registries and abstracts from annual scientific critical care and delirium society meetings. SELECTION CRITERIA: We sought randomized controlled trials (RCTs), including quasi-RCTs, of any pharmacological (drug) for treatment of delirium in critically ill adults. The drug intervention was to be compared to another active drug treatment, placebo, or a non-pharmacological intervention (e.g. mobilization). We did not apply any restrictions in terms of drug class, dose, route of administration, or duration of delirium or drug exposure. We defined critically ill patients as those treated in an ICU of any specialty (e.g. burn, cardiac, medical, surgical, trauma) or high-dependency unit. DATA COLLECTION AND ANALYSIS: Two review authors independently identified studies from the search results; four review authors (in pairs) performed data extraction and assessed risk of bias independently. We performed data synthesis through pairwise meta-analysis and network meta-analysis (NMA). Our hypothetical network structure was designed to be analysed at the drug class level and illustrated a network diagram of 'nodes' (i.e. drug classes) and 'edges' (i.e. comparisons between different drug classes from existing trials), thus describing a treatment network of all possible comparisons between drug classes. We assessed the quality of the body of evidence according to GRADE, as very low, low, moderate, or high. MAIN RESULTS: We screened 7674 citations, from which 14 trials with 1844 participants met our inclusion criteria. Ten RCTs were placebo-controlled, and four reported comparisons of different drugs. Drugs examined in these trials were the following: antipsychotics (n = 10), alpha2 agonists (n = 3; all dexmedetomidine), statins (n = 2), opioids (n = 1; morphine), serotonin antagonists (n = 1; ondansetron), and cholinesterase (CHE) inhibitors (n = 1; rivastigmine). Only one of these trials consistently used non-pharmacological interventions that are known to improve patient outcomes in both intervention and control groups.Eleven studies (n = 1153 participants) contributed to analysis of the primary outcome. Results of the NMA showed that the intervention with the smallest ratio of means (RoM) (i.e. most preferred) compared with placebo was the alpha2 agonist dexmedetomidine (0.58; 95% credible interval (CrI) 0.26 to 1.27; surface under the cumulative ranking curve (SUCRA) 0.895; moderate-quality evidence). In order of descending SUCRA values (best to worst), the next best interventions were atypical antipsychotics (RoM 0.80, 95% CrI 0.50 to 1.11; SUCRA 0.738; moderate-quality evidence), opioids (RoM 0.88, 95% CrI 0.37 to 2.01; SUCRA 0.578; very-low quality evidence), and typical antipsychotics (RoM 0.96, 95% CrI 0.64 to1.36; SUCRA 0.468; high-quality evidence).The NMAs of multiple secondary outcomes revealed that only the alpha2 agonist dexmedetomidine was associated with a shorter duration of mechanical ventilation (RoM 0.55, 95% CrI 0.34 to 0.89; moderate-quality evidence), and the CHE inhibitor rivastigmine was associated with a longer ICU stay (RoM 2.19, 95% CrI 1.47 to 3.27; moderate-quality evidence). Adverse events often were not reported in these trials or, when reported, were rare; pair-wise analysis of QTc prolongation in seven studies did not show significant differences between antipsychotics, ondansetron, dexmedetomidine, and placebo. AUTHORS' CONCLUSIONS: We identified trials of varying quality that examined six different drug classes for treatment of delirium in critically ill adults. We found evidence that the alpha2 agonist dexmedetomidine may shorten delirium duration, although this small effect (compared with placebo) was seen in pairwise analyses based on a single study and was not seen in the NMA results. Alpha2 agonists also ranked best for duration of mechanical ventilation and length of ICU stay, whereas the CHE inhibitor rivastigmine was associated with longer ICU stay. We found no evidence of a difference between placebo and any drug in terms of delirium-free and coma-free days, days with coma, physical restraint use, length of stay, long-term cognitive outcomes, or mortality. No studies reported delirium relapse, resolution of symptoms, or quality of life. The ten ongoing studies and the six studies awaiting classification that we identified, once published and assessed, may alter the conclusions of the review.

Vitamin C to Improve Organ Dysfunction in Cardiac Surgery Patients-Review and Pragmatic Approach.

The pleiotropic biochemical and antioxidant functions of vitamin C have sparked recent interest in its application in intensive care. Vitamin C protects important organ systems (cardiovascular, neurologic and renal systems) during inflammation and oxidative stress. It also influences coagulation and inflammation; its application might prevent organ damage. The current evidence of vitamin C's effect on pathophysiological reactions during various acute stress events (such as sepsis, shock, trauma, burn and ischemia-reperfusion injury) questions whether the application of vitamin C might be especially beneficial for cardiac surgery patients who are routinely exposed to ischemia/reperfusion and subsequent inflammation, systematically affecting different organ systems. This review covers current knowledge about the role of vitamin C in cardiac surgery patients with focus on its influence on organ dysfunctions. The relationships between vitamin C and clinical health outcomes are reviewed with special emphasis on its application in cardiac surgery. Additionally, this review pragmatically discusses evidence on the administration of vitamin C in every day clinical practice, tackling the issues of safety, monitoring, dosage, and appropriate application strategy.

Cough augmentation techniques for extubation or weaning critically ill patients from mechanical ventilation.

BACKGROUND: There are various reasons why weaning and extubation failure occur, but ineffective cough and secretion retention can play a significant role. Cough augmentation techniques, such as lung volume recruitment or manually- and mechanically-assisted cough, are used to prevent and manage respiratory complications associated with chronic conditions, particularly neuromuscular disease, and may improve short- and long-term outcomes for people with acute respiratory failure. However, the role of cough augmentation to facilitate extubation and prevent post-extubation respiratory failure is unclear. OBJECTIVES: Our primary objective was to determine extubation success using cough augmentation techniques compared to no cough augmentation for critically-ill adults and children with acute respiratory failure admitted to a high-intensity care setting capable of managing mechanically-ventilated people (such as an intensive care unit, specialized weaning centre, respiratory intermediate care unit, or high-dependency unit).Secondary objectives were to determine the effect of cough augmentation techniques on reintubation, weaning success, mechanical ventilation and weaning duration, length of stay (high-intensity care setting and hospital), pneumonia, tracheostomy placement and tracheostomy decannulation, and mortality (high-intensity care setting, hospital, and after hospital discharge). We evaluated harms associated with use of cough augmentation techniques when applied via an artificial airway (or non-invasive mask once extubated/decannulated), including haemodynamic compromise, arrhythmias, pneumothorax, haemoptysis, and mucus plugging requiring airway change and the type of person (such as those with neuromuscular disorders or weakness and spinal cord injury) for whom these techniques may be efficacious. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 4, 2016), MEDLINE (OvidSP) (1946 to April 2016), Embase (OvidSP) (1980 to April 2016), CINAHL (EBSCOhost) (1982 to April 2016), and ISI Web of Science and Conference Proceedings. We searched the PROSPERO and Joanna Briggs Institute databases, websites of relevant professional societies, and conference abstracts from five professional society annual congresses (2011 to 2015). We did not impose language or other restrictions. We performed a citation search using PubMed and examined reference lists of relevant studies and reviews. We contacted corresponding authors for details of additional published or unpublished work. We searched for unpublished studies and ongoing trials on the International Clinical Trials Registry Platform (apps.who.int/trialsearch) (April 2016). SELECTION CRITERIA: We included randomized and quasi-randomized controlled trials that evaluated cough augmentation compared to a control group without this intervention. We included non-randomized studies for assessment of harms. We included studies of adults and of children aged four weeks or older, receiving invasive mechanical ventilation in a high-intensity care setting. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts identified by our search methods. Two review authors independently evaluated full-text versions, independently extracted data and assessed risks of bias. MAIN RESULTS: We screened 2686 citations and included two trials enrolling 95 participants and one cohort study enrolling 17 participants. We assessed one randomized controlled trial as being at unclear risk of bias, and the other at high risk of bias; we assessed the non-randomized study as being at high risk of bias. We were unable to pool data due to the small number of studies meeting our inclusion criteria and therefore present narrative results rather than meta-analyses. One trial of 75 participants reported that extubation success (defined as no need for reintubation within 48 hours) was higher in the mechanical insufflation-exsufflation (MI-E) group (82.9% versus 52.5%, P < 0.05) (risk ratio (RR) 1.58, 95% confidence interval (CI) 1.13 to 2.20, very low-quality evidence). No study reported weaning success or reintubation as distinct from extubation success. One trial reported a statistically significant reduction in mechanical ventilation duration favouring MI-E (mean difference -6.1 days, 95% CI -8.4 to -3.8, very low-quality evidence). One trial reported mortality, with no participant dying in either study group. Adverse events (reported by two trials) included one participant receiving the MI-E protocol experiencing haemodynamic compromise. Nine (22.5%) of the control group compared to two (6%) MI-E participants experienced secretion encumbrance with severe hypoxaemia requiring reintubation (RR 0.25, 95% CI 0.06 to 1.10). In the lung volume recruitment trial, one participant experienced an elevated blood pressure for more than 30 minutes. No participant experienced new-onset arrhythmias, heart rate increased by more than 25%, or a pneumothorax.For outcomes assessed using GRADE, we based our downgrading decisions on unclear risk of bias, inability to assess consistency or publication bias, and uncertainty about the estimate of effect due to the limited number of studies contributing outcome data. AUTHORS' CONCLUSIONS: The overall quality of evidence on the efficacy of cough augmentation techniques for critically-ill people is very low. Cough augmentation techniques when used in mechanically-ventilated critically-ill people appear to result in few adverse events.

Development of an intensive care unit resource assessment survey for the care of critically ill patients in resource-limited settings.

PURPOSE: Capacity to provide critical care in resource-limited settings is poorly understood because of lack of data about resources available to manage critically ill patients. Our objective was to develop a survey to address this issue. METHODS: We developed and piloted a cross-sectional self-administered survey in 9 resource-limited countries. The survey consisted of 8 domains; specific items within domains were modified from previously developed survey tools. We distributed the survey by e-mail to a convenience sample of health care providers responsible for providing care to critically ill patients. We assessed clinical sensibility and test-retest reliability. RESULTS: Nine of 15 health care providers responded to the survey on 2 separate occasions, separated by 2 to 4 weeks. Clinical sensibility was high (3.9-4.9/5 on assessment tool). Test-retest reliability for questions related to resource availability was acceptable (intraclass correlation coefficient, 0.94; 95% confidence interval, 0.75-0.99; mean (SD) of weighted κ values = 0.67 [0.19]). The mean (SD) time for survey completion survey was 21 (16) minutes. CONCLUSIONS: A reliable cross-sectional survey of available resources to manage critically ill patients can be feasibly administered to health care providers in resource-limited settings. The survey will inform future research focusing on access to critical care where it is poorly described but urgently needed.

Effect of thromboelastography (TEG®) and rotational thromboelastometry (ROTEM®) on diagnosis of coagulopathy, transfusion guidance and mortality in trauma: descriptive systematic review.

INTRODUCTION: The understanding of coagulopathies in trauma has increased interest in thromboelastography (TEG®) and thromboelastometry (ROTEM®), which promptly evaluate the entire clotting process and may guide blood product therapy. Our objective was to review the evidence for their role in diagnosing early coagulopathies, guiding blood transfusion, and reducing mortality in injured patients. METHODS: We considered observational studies and randomized controlled trials (MEDLINE, EMBASE, and Cochrane databases) to February 2014 that examined TEG®/ROTEM® in adult trauma patients. We extracted data on demographics, diagnosis of early coagulopathies, blood transfusion, and mortality. We assessed methodologic quality by using the Newcastle-Ottawa scale (NOS) for observational studies and QUADAS-2 tool for diagnostic accuracy studies. RESULTS: Fifty-five studies (12,489 patients) met inclusion criteria, including 38 prospective cohort studies, 15 retrospective cohort studies, two before-after studies, and no randomized trials. Methodologic quality was moderate (mean NOS score, 6.07; standard deviation, 0.49). With QUADAS-2, only three of 47 studies (6.4%) had a low risk of bias in all domains (patient selection, index test, reference standard and flow and timing); 37 of 47 studies (78.8%) had low concerns regarding applicability. Studies investigated TEG®/ROTEM® for diagnosis of early coagulopathies (n = 40) or for associations with blood-product transfusion (n = 25) or mortality (n = 24). Most (n = 52) were single-center studies. Techniques examined included rapid TEG® (n =12), ROTEM® (n = 18), TEG® (n = 23), or both TEG® and rapid TEG® (n = 2). Many TEG®/ROTEM® measurements were associated with early coagulopathies, including some (hypercoagulability, hyperfibrinolysis, platelet dysfunction) not assessed by routine screening coagulation tests. Standard measures of diagnostic accuracy were inconsistently reported. Many abnormalities predicted the need for massive transfusion and death, but predictive performance was not consistently superior to routine tests. One observational study suggested that a ROTEM®-based transfusion algorithm reduced blood-product transfusion, but TEG®/ROTEM®-based resuscitation was not associated with lower mortality in most studies. CONCLUSIONS: Limited evidence from observational data suggest that TEG®/ROTEM® tests diagnose early trauma coagulopathy and may predict blood-product transfusion and mortality in trauma. Effects on blood-product transfusion, mortality, and other patient-important outcomes remain unproven in randomized trials.

Acute refractory hypoxemia after chest trauma reversed by high-frequency oscillatory ventilation: a case report.

INTRODUCTION: Polytrauma often results in significant hypoxemia secondary to direct lung contusion or indirectly through atelectasis, systemic inflammatory response, large volume fluid resuscitation and blood product transfusion. In addition to causing hypoxemia, atelectasis and acute lung injury can lead to right ventricular failure through an acute increase in pulmonary vascular resistance. Mechanical ventilation is often applied, accompanied with recruitment maneuvers and positive end-expiratory pressure in order to recruit alveoli and reverse atelectasis, while preventing excessive alveolar damage. This strategy should lead to the reversal of the hypoxemic condition and the detrimental heart-lung interaction that may occur. However, as described in this case report, hemodynamic instability and intractable alveolar atelectasis sometimes do not respond to conventional ventilation strategies. CASE PRESENTATION: We describe the case of a 21-year-old Caucasian man with severe chest trauma requiring surgical interventions, who developed refractory hypoxemia and overt right ventricular failure. After multiple failed attempts of recruitment using conventional ventilation, the patient was ventilated with high-frequency oscillatory ventilation. This mode of ventilation allowed the reversal of the hemodynamic effects of severe hypoxemia and of the acute cor pulmonale. We use this case report to describe the physiological advantages of high-frequency oscillatory ventilation in patients with chest trauma, and formulate the arguments to explain the positive effect observed in our patient. CONCLUSIONS: High-frequency oscillatory ventilation can be used in the context of a blunt chest trauma accompanied by severe hypoxemia due to atelectasis. The positive effect is due to its capacity to recruit the collapsed alveoli and, as a result, the relief of increased pulmonary vascular resistance and subsequently the reversal of acute cor pulmonale. This approach may represent an alternative in case of failure of the conventional ventilation strategy.

Critical care resources in the Solomon Islands: a cross-sectional survey.

BACKGROUND: There are minimal data available on critical care case-mix, care processes and outcomes in lower and middle income countries (LMICs). The objectives of this paper were to gather data in the Solomon Islands in order to gain a better understanding of common presentations of critical illness, available hospital resources, and what resources would be helpful in improving the care of these patients in the future. METHODS: This study used a mixed methods approach, including a cross sectional survey of respondents' opinions regarding critical care needs, ethnographic information and qualitative data. RESULTS: The four most common conditions leading to critical illness in the Solomon Islands are malaria, diseases of the respiratory system including pneumonia and influenza, diabetes mellitus and tuberculosis. Complications of surgery and trauma less frequently result in critical illness. Respondents emphasised the need for basic critical care resources in LMICs, including equipment such as oximeters and oxygen concentrators; greater access to medications and blood products; laboratory services; staff education; and the need for at least one national critical care facility. CONCLUSIONS: A large degree of critical illness in LMICs is likely due to inadequate resources for primary prevention and healthcare; however, for patients who fall through the net of prevention, there may be simple therapies and context-appropriate resources to mitigate the high burden of morbidity and mortality. Emphasis should be on the development and acquisition of simple and inexpensive tools rather than complicated equipment, to prevent critical care from unduly diverting resources away from other important parts of the health system.

Noninvasive positive pressure ventilation as a weaning strategy for intubated adults with respiratory failure.

BACKGROUND: Noninvasive positive pressure ventilation (NPPV) provides ventilatory support without the need for an invasive airway approach. Interest has emerged in using NPPV to facilitate earlier removal of an endotracheal tube and decrease complications associated with prolonged intubation. OBJECTIVES: To summarize the evidence comparing NPPV and invasive positive pressure ventilation (IPPV) weaning on clinical outcomes in intubated adults with respiratory failure. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2008), MEDLINE (January 1966 to April 2008), EMBASE (January 1980 to April 2008), proceedings from four conferences, and personal files; and contacted authors to identify randomized controlled trials comparing NPPV and IPPV weaning. SELECTION CRITERIA: Randomized and quasi-randomized studies comparing early extubation with immediate application of NPPV to IPPV weaning in intubated adults with respiratory failure. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and abstracted data according to prespecified criteria. Sensitivity and subgroup analyses were planned to assess the impact of (i) excluding quasi-randomized trials, and (ii) the etiology of respiratory failure on selected outcomes. MAIN RESULTS: We identified 12 trials of moderate to good quality that involved 530 participants with predominantly chronic obstructive pulmonary disease (COPD). Compared to the IPPV strategy, NPPV significantly decreased mortality (relative risk (RR) 0.55, 95% confidence Interval (CI) 0.38 to 0.79), ventilator associated pneumonia (RR 0.29, 95% CI 0.19 to 0.45), length of stay in an intensive care unit (weighted mean difference (WMD) -6.27 days, 95% CI -8.77 to -3.78) and hospital (WMD -7.19 days, 95% CI -10.80 to -3.58), total duration of ventilation (WVD) -5.64 days (95% CI -9.50 to -1.77) and duration of endotracheal mechanical ventilation (WMD - 7.81 days, 95% CI -11.31 to -4.31). Noninvasive weaning had no effect on weaning failures or the duration of ventilation related to weaning. Excluding a single quasi-randomized trial maintained the significant reduction in mortality and ventilator associated pneumonia. Subgroup analyses suggested that the benefits on mortality and weaning failures were nonsignificantly greater in trials enrolling exclusively COPD patients versus mixed populations. AUTHORS' CONCLUSIONS: Summary estimates from 12 small studies of moderate to good quality that included predominantly COPD patients demonstrated a consistent, positive effect on mortality and ventilator associated pneumonia. The net clinical benefits associated with noninvasive weaning remain to be fully elucidated.