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Background Several repurposed drugs such as hydroxychloroquine (HCQ) have been investigated for treatment of COVID-19, but none was confirmed to be efficacious. While in vitro studies have demonstrated antiviral properties of HCQ, data from clinical trials were conflicting regarding its benefit for COVID-19 treatment. Drugs that limit viral replication may be beneficial in the earlier course of the disease thus slowing progression to severe and critical illness. Design We conducted a randomized open label Phase II clinical trial from October–December 2020. Methods Patients diagnosed with COVID-19 using RT-PCR were included in the study if they were 18 years and above and had a diagnosis of COVID-19 made in the last 3 days. Patients were randomized in blocks, to receive either HCQ 400 mg twice a day for the first day followed by 200 mg twice daily for the next 4 days plus standard of care (SOC) treatment or SOC treatment alone. SARS COV-2 viral load (CT values) from RT-PCR testing of samples collected using nasal/orapharyngeal swabs was performed at baseline, day 2, 4, 6, 8 and 10. The primary outcome was median time from randomization to SARS COV-2 viral clearance by day 6. Results Of the 105 participants enrolled, 55 were assigned to the intervention group (HCQ plus SOC) and 50 to the control group (SOC only). Baseline characteristics were similar across treatment arms. Viral clearance did not differ by treatment arm, 20 and 19 participants respectively had SARS COV-2 viral load clearance by day 6 with no significant difference, median (IQR) number of days to viral load clearance between the two groups was 4(3–4) vs 4(2–4): p = 0.457. There were no significant differences in secondary outcomes (symptom resolution and adverse events) between the intervention group and the control group. There were no significant differences in specific adverse events such as elevated alkaline phosphatase, prolonged QTc interval on ECG, among patients in the intervention group as compared to the control group. Conclusion Our results show that HCQ 400 mg twice a day for the first day followed by 200 mg twice daily for the next 4 days was safe but not associated with reduction in viral clearance or symptom resolution among adults with COVID-19 in Uganda. Trial registration: NCT04860284.

ARDS is a life-threatening form of respiratory failure accounting for at least 10% of global ICU admissions (1-5). The Berlin definition for diagnosing ARDS, is expensive for most resource-constrained settings to apply(6-8). There are therefore very limited data reporting on the burden of ARDS in Low-income countries (LICs). We sought to determine the prevalence of ARDS among mechanically ventilated Ugandan intensive care unit (ICU) patients using the Kigali modification.

Purpose To describe the organizational characteristics of functional ICUs in Uganda. Methods A descriptive survey of 12 ICUs in Uganda; ICU organisation, structure, staffing, and support facilities. A functional ICU was defined as one that admitted critically ill patients and had the ability to provide mechanical ventilation. ICUs were selected based on information of their existence. Direct structured interviews were carried out with the ICU directors. Results Of the fourteen ICUs reviewed, 12 were functional, and a majority were located in the central region. There were 55 ICU beds making up a ratio of 1.3 ICU beds per million population. The ICU beds comprised 1.5 % of the total bed capacity of studied hospitals. Most of the ICUs [11] were mixed (paediatric-adults), anaesthesia-led (nine) and five operated in a closed model. There were 171 ICU nurses, of whom 13 had formal training in critical care nursing. The majority of the ICUs had a nurse to patient ratio ≥ 1.2; nine during the day and seven at night. Conclusions This study shows limited accessibility to critical care services in Uganda. With a high variability in the ICU operational characteristics, there is a need for standardization of ICU care in the country.

Background\ud Sepsis poses a global threat to millions of lives. The Surviving Sepsis Campaign (SSC) guidelines provide evidence-based recommendations on the recognition and management of sepsis and its complications.\ud Methods\ud We formed a panel of 60 experts from 22 countries and 11 members of the public. The panel prioritized questions that are relevant to the recognition and management of sepsis and septic shock in adults. New questions and sections were addressed, relative to the previous guidelines. These questions were grouped under 6 subgroups (screening and early treatment, infection, hemodynamics, ventilation, additional therapies, and long-term outcomes and goals of care). With input from the panel and methodologists, professional medical librarians performed the search strategy tailored to either specific questions or a group of relevant questions. A dedicated systematic review team performed screening and data abstraction when indicated. For each question, the methodologists, with input from panel members, summarized the evidence assessed and graded the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. The panel generated recommendations using the evidence-to-decision framework. Recommendations were either strong or weak, or in the form of best practice statements. When evidence was insufficient to support a recommendation, the panel was surveyed to generate “in our practice” statements.\ud Results\ud The SSC panel issued 93 statements: 15 best practice statements, 15 strong recommendations, and 54 weak recommendations and no recommendation was provided for 9 questions. The recommendations address several important clinical areas related to screening tools, acute resuscitation strategies, management of fluids and vasoactive agents, antimicrobials and diagnostic tests and the use of additional therapies, ventilation management, goals of care, and post sepsis care.\ud Conclusion\ud The SSC panel issued evidence-based recommendations to help support key stakeholders caring for adults with sepsis or septic shock and their families.

Background A pilot study on the World Health Organization (WHO) Surgical Safety Checklist (SSC) showed a reduction in both major complications and mortality of surgical patients. Compliance with this checklist varies around the world. We aimed to determine the extent of compliance with the WHO SSC and its association with surgical outcomes in 5 of Uganda's referral hospitals. Methods A multicentre prospective cohort study was conducted in 5 referral hospitals in Uganda. Using a questionnaire based on the WHO SSC, patients undergoing surgical operations were systematically recruited into the study from April 2016 to July 2016. The patients were followed up daily for 30 days or until discharge for the purpose of documentation of complications. Logistic regression and linear regression were used to assess for association between compliance and perioperative surgical outcomes. Results We recruited 859 patients into the study. Overall compliance with the WHO SSC was 41.7% (95% confidence interval [CI], 39.7-43.8) ranging from 11.9% to 89.8% across the different hospitals. Overall compliance with "sign in" was 44.7% (95% CI, 43-45.6), with "time out" was 42.0% (95% CI, 39.4-44.6), and with "sign out" was 33.3% (95% CI, 30.7-35.9). There was no association between compliance and perioperative surgical outcomes: length of hospital stay, adverse events, and mortality. Conclusions This study revealed low levels of compliance with the WHO SSC. There was a statistically significant association between this level of compliance and the incidence of pain and loss of consciousness postoperatively.

This is the twelfth version (eleventh update) of the living guideline, replacing earlier versions (available as data supplements). New recommendations will be published as updates to this guideline.What is the role of drugs in the treatment of patients with covid-19?The evidence base for therapeutics for covid-19 is evolving with numerous randomised controlled trials (RCTs) recently completed and under way. The emerging SARS-CoV-2 variants (such as omicron) and subvariants are also changing the role of therapeutics. This update provides updated recommendations for remdesivir, addresses the use of combination therapy with corticosteroids, interleukin-6 (IL-6) receptor blockers, and janus kinase (JAK) inhibitors in patients with severe or critical covid-19, and modifies previous recommendations for the neutralising monoclonal antibodies sotrovimab and casirivimab-imdevimab in patients with non-severe covid-19.• Remdesivir: a conditional recommendation for its use in patients with severe covid-19; and a conditional recommendation against its use in patients with critical covid-19. • Concomitant use of IL-6 receptor blockers (tocilizumab or sarilumab) and the JAK inhibitor baricitinib: these drugs may now be combined, in addition to corticosteroids, in patients with severe or critical covid-19. • Sotrovimab and casirivimab-imdevimab: strong recommendations against their use in patients with covid-19, replacing the previous conditional recommendations for their use.When moving from new evidence to updated recommendations, the Guideline Development Group (GDG) considered a combination of evidence assessing relative benefits and harms, values and preferences, and feasibility issues. For remdesivir, new trial data were added to a previous subgroup analysis and provided sufficiently trustworthy evidence to demonstrate benefits in patients with severe covid-19, but not critical covid-19. The GDG considered benefits of remdesivir to be modest and of moderate certainty for key outcomes such as mortality and mechanical ventilation, resulting in a conditional recommendation. For baricitinib, the GDG considered clinical trial evidence (RECOVERY) demonstrating reduced risk of death in patients already receiving corticosteroids and IL-6 receptor blockers. The GDG acknowledged that the clinical trials were not representative of the world population and that the risk-benefit balance may be less advantageous, particularly in patients who are immunosuppressed at higher risk of opportunistic infections (such as serious fungal, viral, or bacteria), those already deteriorating where less aggressive or stepwise addition of immunosuppressive medications may be preferred, and in areas where certain pathogens such as HIV or tuberculosis, are of concern. The panel anticipated that there would be situations where clinicians may opt for less aggressive immunosuppressive therapy or to combine medications in a stepwise fashion in patients who are deteriorating. The decision to combine the medications will depend on their availability, and the treating clinician's perception of the risk-benefit balance associated with combination immunosuppressive therapy, particularly in patient populations at risk of opportunistic infections who may have been under-represented in clinical trials. When making a strong recommendation against the use of monoclonal antibodies for patients with covid-19, the GDG considered in vitro neutralisation data demonstrating that sotrovimab and casirivimab-imdevimab evaluated in clinical trials have meaningfully reduced neutralisation activity of the currently circulating variants of SARS-CoV-2 and their subvariants. There was consensus among the panel that the absence of in vitro neutralisation activity strongly suggests absence of clinical effectiveness of these monoclonal antibodies. However, there was also consensus regarding the need for clinical trial evidence in order to confirm clinical efficacy of new monoclonal antibodies that reliably neutralise the circulating strains in vitro. Whether emerging new variants and subvariants might be susceptible to sotrovimab, casirivimab-imdevimab, or other anti-SARS-CoV-2 monoclonal antibodies cannot be predicted.• Recommended for patients with severe or critical covid-19—strong recommendations for systemic corticosteroids; IL-6 receptor blockers (tocilizumab or sarilumab) in combination with corticosteroids; and baricitinib as an alternative to IL-6 receptor blockers, in combination with corticosteroids. • Recommended for patients with non-severe covid-19 at highest risk of hospitalisation—a strong recommendation for nirmatrelvir/ritonavir; conditional recommendations for molnupiravir and remdesivir. • Not recommended for patients with non-severe covid-19—a conditional recommendation against systemic corticosteroids; a strong recommendation against convalescent plasma; a recommendation against fluvoxamine, except in the context of a clinical trial; and a strong recommendation against colchicine. • Not recommended for patients with non-severe covid-19 at low risk of hospitalisation—a conditional recommendation against nirmatrelvir/ritonavir. • Not recommended for patients with severe or critical covid-19—a recommendation against convalescent plasma except in the context of a clinical trial; and a conditional recommendation against the JAK inhibitors ruxolitinib and tofacitinib. • Not recommended, regardless of covid-19 disease severity—a strong recommendations against hydroxychloroquine and against lopinavir/ritonavir; and a recommendation against ivermectin except in the context of a clinical trial.This living guideline from the World Health Organization (WHO) incorporates new evidence to dynamically update recommendations for covid-19 therapeutics. The GDG typically evaluates a therapy when the WHO judges sufficient evidence is available to make a recommendation. While the GDG takes an individual patient perspective in making recommendations, it also considers resource implications, acceptability, feasibility, equity, and human rights. This guideline was developed according to standards and methods for trustworthy guidelines, making use of an innovative process to achieve efficiency in dynamic updating of recommendations. The methods are aligned with the WHO Handbook for Guideline Development and according to a pre-approved protocol (planning proposal) by the Guideline Review Committee (GRC). A box at the end of the article outlines key methodological aspects of the guideline process. MAGIC Evidence Ecosystem Foundation provides methodological support, including the coordination of living systematic reviews with network meta-analyses to inform the recommendations. The full version of the guideline is available online in MAGICapp and in PDF, with a summary version here in The BMJ. These formats should facilitate adaptation, which is strongly encouraged by WHO to contextualise recommendations in a healthcare system to maximise impact.Recommendations on anticoagulation are planned for the next update to this guideline.

Clinical question What is the role of drugs in preventing covid-19? Why does this matter? There is widespread interest in whether drug interventions can be used for the prevention of covid-19, but there is uncertainty about which drugs, if any, are effective. Recommendations The second version of this living guideline reiterates the previous strong recommendation against the use of hydroxychloroquine and includes a new conditional recommendation against the use of tixagevimab-cilgavimab in individuals who do not have covid-19. How this guideline was created This living guideline is from the World Health Organization (WHO) and provides up to date covid-19 guidance to inform policy and practice worldwide. Magic Evidence Ecosystem Foundation (MAGIC) provides methodological support. A living systematic review with network analysis informs the recommendations. An international guideline development group (GDG) of content experts, clinicians, patients, an ethicist and methodologists produces recommendations following standards for trustworthy guideline development using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Understanding the recommendations The living network meta-analysis informing this guideline included 12 trials (8379 participants) comparing hydroxychloroquine to standard care/placebo, and one trial (5197 participants) comparing tixagevimab-cilgavimab to standard care/placebo. When moving from evidence to the continued strong recommendation against the use of hydroxychloroquine, the GDG emphasised additional evidence suggesting no or little effect on mortality and hospital admission, and an increased risk of adverse effects. For the new conditional recommendation against the use of tixagevimab-cilgavimab, the GDG emphasised in vitro evidence reducing the applicability of available trial data. While trial results demonstrated modest reduction in the occurrence of laboratory confirmed symptomatic covid-19, lack of in vitro neutralisation of new SARS-CoV-2 sub-lineages was considered to have rendered these results obsolete. Updates This is a living guideline. New recommendations will be published in this article and signposted by update notices to this guideline. Readers note This is the second version of the living guideline for drugs to prevent covid-19. It complements the WHO living guideline on drugs to treat covid-19 and living guidance regarding covid-19 related clinical management. When citing this article, please consider adding the update number and date of access for clarity.

Clinical questionWhat is the role of remdesivir in the treatment of severe covid-19? This guideline was triggered by the ACTT-1 trial published in the New England Journal of Medicine on 22 May 2020.Current practiceRemdesivir has received worldwide attention as a potentially effective treatment for severe covid-19. After rapid market approval in the US, remdesivir is already being used in clinical practice.RecommendationsThe guideline panel makes a weak recommendation for the use of remdesivir in severe covid-19 while recommending continuation of active enrolment of patients into ongoing randomised controlled trials examining remdesivir.How this guideline was createdAn international panel of patients, clinicians, and methodologists produced these recommendations in adherence with standards for trustworthy guidelines using the GRADE approach. The recommendations are based on a linked systematic review and network meta-analysis. The panel considered an individual patient perspective and allowed contextual factors (such as resources) to be taken into account for countries and healthcare systems.The evidenceThe linked systematic review (published 31 Jul 2020) identified two randomised trials with 1300 participants, showing low certainty evidence that remdesivir may be effective in reducing time to clinical improvement and may decrease mortality in patients with severe covid-19. Remdesivir probably has no important effect on need for invasive mechanical ventilation. Remdesivir may have little or no effect on hospital length of stay.Understanding the recommendationMost patients with severe covid-19 would likely choose treatment with remdesivir given the potential reduction in time to clinical improvement. However, given the low certainty evidence for critical outcomes and the fact that different perspectives, values, and preferences may alter decisions regarding remdesivir, the panel issued a weak recommendation with strong support for continued recruitment in randomised trials.

IntroductionLimited data exist on the epidemiology of acute hypoxaemic respiratory failure (AHRF) in low-income countries (LICs). We sought to determine the prevalence of AHRF in critically ill adult patients admitted to a Ugandan tertiary referral hospital; determine clinical and treatment characteristics as well as assess factors associated with mortality.Materials and methodsWe conducted a prospective observational study at the Mulago National Referral and Teaching Hospital in Uganda. Critically ill adults who were hospitalised at the emergency department and met the criteria for AHRF (acute shortness of breath for less than a week) were enrolled and followed up for 90 days. Multivariable analyses were conducted to determine the risk factors for death.ResultsA total of 7300 patients was screened. Of these, 327 (4.5%) presented with AHRF. The majority (60 %) was male and the median age was 38 years (IQR 27–52). The mean plethysmographic oxygen saturation (SpO2) was 77.6% (SD 12.7); mean SpO2/FiO2 ratio 194 (SD 32) and the mean Lung Injury Prediction Score (LIPS) 6.7 (SD 0.8). Pneumonia (80%) was the most common diagnosis. Only 6% of the patients received mechanical ventilatory support. In-hospital mortality was 77% with an average length of hospital stay of 9.2 days (SD 7). At 90 days after enrolment, the mortality increased to 85%. Factors associated with mortality were severity of hypoxaemia (risk ratio (RR) 1.29 (95% CI 1.15 to 1.54), p=0.01); a high LIPS (RR 1.79 (95% CI 1.79 1.14 to 2.83), p=0.01); thrombocytopenia (RR 1.23 (95% CI 1.11 to 1.38), p=0.01); anaemia (RR 1.15 (95% CI 1.01 to 1.31), p=0.03) ; HIV co-infection (RR 0.84 (95% CI 0.72 to 0.97), p=0.019) and male gender (RR 1.15 (95% CI 1.01 to 1.31) p=0.04).ConclusionsThe prevalence of AHRF among emergency department patients in a tertiary hospital in an LIC was low but was associated with very high mortality. Pneumonia was the most common cause of AHRF. Mortality was associated with higher severity of hypoxaemia, high LIPS, anaemia, HIV co-infection, thrombocytopenia and being male.

Objective To assess the value of the inability to walk unassisted to predict hospital mortality in patients with suspected infection in a resource-limited setting. Methods This is a post hoc study of a prospective trial performed in rural Rwanda. Patients hospitalized because of a suspected acute infection and who were able to walk unassisted before this disease episode were included. At hospital presentation, the walking status was graded into: 1) can walk unassisted, 2) can walk assisted only, 3) cannot walk. Receiver operating characteristic (ROC) analyses and two-by-two tables were used to determine the sensitivity, specificity, negative and positive predictive values of the inability to walk unassisted to predict in-hospital death. Results One-thousand-sixty-nine patients were included. Two-hundred-one (18.8%), 315 (29.5%), and 553 (51.7%) subjects could walk unassisted, walk assisted or not walk, respectively. Their hospital mortality was 0%, 3.8% and 6.3%, respectively. The inability to walk unassisted had a low specificity (20%) but was 100% sensitive (CI95%, 90–100%) to predict in-hospital death (p = 0.00007). The value of the inability to walk unassisted to predict in-hospital mortality (AUC ROC, 0.636; CI95%, 0.564–0.707) was comparable to that of the qSOFA score (AUC ROC, 0.622; CI95% 0.524–0.728). Fifteen (7.5%), 34 (10.8%) and 167 (30.2%) patients who could walk unassisted, walk assisted or not walk presented with a qSOFA score count ≥2 points, respectively (p

To deploy machine learning tools (random forests) to develop a model that reliably predicts hospital mortality in children with acute infections residing in low- and middle-income countries, using age and other variables collected at hospital admission.Post hoc analysis of a single-center, prospective, before-and-after feasibility trial.Rural district hospital in Rwanda, a low-income country in Sub-Sahara Africa.Infants and children greater than 28 days and less than 18 years of life hospitalized because of an acute infection.None.Age, vital signs (heart rate, respiratory rate, and temperature) capillary refill time, altered mental state collected at hospital admission, as well as survival status at hospital discharge were extracted from the trial database. This information was collected for 1,579 adult and pediatric patients admitted to a regional referral hospital with an acute infection in rural Rwanda. Nine-hundred forty-nine children were included in this analysis. We predicted survival in study subjects using random forests, a machine learning algorithm. Five prediction models, all including age plus two to five other variables, were tested. Three distinct optimization criteria of the algorithm were then compared. The in-hospital mortality was 1.5% (n = 14). All five models could predict in-hospital mortality with an area under the receiver operating characteristic curve ranging between 0.69 and 0.8. The model including age, respiratory rate, capillary refill time, altered mental state exhibited the highest predictive value area under the receiver operating characteristic curve 0.8 (95% CI, 0.78-0.8) with the lowest possible number of variables.A machine learning-based algorithm could reliably predict hospital mortality in a Sub-Sahara African population of 949 children with an acute infection using easily collected information at admission which includes age, respiratory rate, capillary refill time, and altered mental state. Future studies need to evaluate and strengthen this algorithm in larger pediatric populations, both in high- and low-/middle-income countries.

OBJECTIVE To evaluate whether a focused education program and implementation of a treatment bundle increases the rate of early evidence-based interventions in patients with acute infections. DESIGN Single-center, prospective, before-and-after feasibility trial. SETTING Emergency department of a sub-Saharan African district hospital. PATIENTS Patients > 28 days of life admitted to the study hospital for an acute infection. INTERVENTIONS The trial had three phases (each of four months). Interventions took place during the second (educational program followed by implementation of the treatment bundle) and third (provision of resources to implement treatment bundle) phases. MEASUREMENTS AND MAIN RESULTS Demographic, clinical, and laboratory data were collected at study enrollment; 24, 48, and 72 hours after hospital admission; and at discharge. A total of 1,594 patients were enrolled (pre-intervention, n = 661; intervention I, n = 531; intervention II, n = 402). The rate of early evidence-based interventions per patient during Intervention Phase I was greater than during the pre-intervention phase (74 ± 17 vs. 79 ± 15%, p < 0.001). No difference was detected when data were compared between Intervention Phases I and II (79 ± 15 vs. 80 ± 15%, p = 0.58). No differences in the incidence of blood transfusion (pre-intervention, 6%; intervention I, 7%; intervention II, 7%) or severe adverse events in the first 24 hours (allergic reactions: pre-intervention, 0.2%; intervention I, 0%; intervention II, 0%; respiratory failure: pre-intervention, 2%; intervention I, 2%; intervention II, 2%; acute renal failure: pre-intervention, 2%; intervention I, 2%; intervention II, 1%) were observed. CONCLUSIONS Our results indicate that a focused education program and implementation of an infection treatment bundle in clinical practice increased the rate of early evidence-based interventions in patients with acute infections (mostly malaria) admitted to a sub-Saharan African district hospital. Provision of material resources did not further increase this rate. While no safety issues were detected, this could be related to the very low disease severity of the enrolled patient population (www.clinicaltrials.gov: NCT02697513).

Tuberculosis (TB) is one of the top ten causes of death worldwide. In 2016, there were 490,000 cases of multi-drug resistant TB globally. Over 2 billion people have asymptomatic latent Mycobacterium tuberculosis infection. TB represents an important, but neglected management issue in patients presenting to intensive care units. Tuberculosis in intensive care settings may present as the primary diagnosis (active drug sensitive or resistant TB disease). In other patients TB may be an incidental co-morbid finding as previously undiagnosed sub-clinical or latent TB which may re-activate under conditions of stress and immunosuppression. In Sub-Saharan Africa, where co-infection with the human immunodeficiency virus and other communicable diseases is highly prevalent, TB is one of the most frequent clinical management issues in all healthcare settings. Acute respiratory failure, septic shock and multi-organ dysfunction are the most common reasons for intensive care unit admission of patients with pulmonary or extrapulmonary TB. Poor absorption of anti-TB drugs occurs in critically ill patients and worsens survival. The mortality of patients requiring intensive care is high. The majority of early TB deaths result from acute cardiorespiratory failure or septic shock. Important clinical presentations, management and infection control issues regarding TB in intensive care settings are reviewed.

Crystalloids are used routinely for perioperative fluid management in cesarean delivery. Few studies have determined the crystalloid of choice in obstetric anesthesia. We compared the effects of Ringer's lactate (RL) versus 0.9% normal saline (NS) on maternal and neonatal blood pH and 24-hour postoperative morbidity in urgent cesarean delivery in a low-resource setting. Our hypothesis was that RL would result in 30% less acidosis than NS.This was a pragmatic prospective double-blind randomized controlled trial in the Mulago National Referral Hospital Labor Ward Theater from September 2011 to May 2012. Five hundred parturients were studied; 252 were randomly assigned to NS and 248 to RL groups. Preoperative and postoperative maternal venous blood gases and placental umbilical arterial cord blood gases were analyzed. The primary outcome was incidence of maternal acidosis, as defined by a postoperative drop in venous pH below 7.32 or reduction in base excess below -3 in a previously normal parturient. Maternal 24-hour postoperative morbidity, neonatal pH, and neonatal base excess were the main secondary outcomes. The study was registered in ClinicalTrials.gov as NCT01585740.The overall incidence of maternal acidosis was 38% in NS and 29% in RL (relative risk, 1.29; 95% confidence interval, 1.01-1.66; P = .04). Thirty-two percent of parturients in NS experienced a drop in venous pH below 7.32 postoperatively, compared with 19% in RL (relative risk, 1.65; 95% confidence interval, 1.18-2.31; P = .003). The comparative drop in base excess postoperatively below -3 between the 2 groups was not statistically significant. There were no significant differences in the incidence of maternal 24-hour postoperative morbidity events and neonatal outcomes between the 2 groups.NS may be a safe choice for intraoperative fluid therapy in urgent cesarean delivery as RL, albeit with an increased incidence of metabolic acidosis.

Sepsis is a major reason for intensive care unit (ICU) admission, also in resource–poor settings. ICUs in low– and middle–income countries (LMICs) face many challenges that could affect patient outcome. The aim of this review is to describe differences between resource–poor and resource–rich settings regarding the epidemiology, pathophysiology, economics and research aspects of sepsis. We restricted this manuscript to the ICU setting even knowing that many sepsis patients in LMICs are treated outside an ICU. Although many bacterial pathogens causing sepsis in LMICs are similar to those in high–income countries, resistance patterns to antimicrobial drugs can be very different; in addition, causes of sepsis in LMICs often include tropical diseases in which direct damaging effects of pathogens and their products can sometimes be more important than the response of the host. There are substantial and persisting differences in ICU capacities around the world; not surprisingly the lowest capacities are found in LMICs, but with important heterogeneity within individual LMICs. Although many aspects of sepsis management developed in rich countries are applicable in LMICs, implementation requires strong consideration of cost implications and the important differences in resources. Addressing both disease–specific and setting–specific factors is important to improve performance of ICUs in LMICs. Although critical care for severe sepsis is likely cost–effective in LMIC setting, more detailed evaluation at both at a macro– and micro–economy level is necessary. Sepsis management in resource–limited settings is a largely unexplored frontier with important opportunities for research, training, and other initiatives for improvement.

Sepsis is a life-threatening condition characterized by one or more organ dysfunctions due to a dysregulated host response to infection [1] or, in certain cases, due to direct pathogen effects. Sepsis is not only associated with bacterial or fungal infections but also with any other infection such as viral disease, protozoal (e.g., malaria), or tropical infections. Although the literature suggests that sepsis is predominantly a healthcare issue in resource-rich countries, the global burden of acute infections is highest in resource-limited areas [2]. Successful sepsis management relies on various components of which early recognition is essential. Evidence and recommendations for sepsis recognition are mainly based on research performed in resource-rich settings [3]. However, resource-rich and -limited countries differ in healthcare accessibility [4] and infectious disease epidemiology [5–7]. It is therefore unreasonable to directly translate evidence between these settings. The Global Intensive Care working group of the European Society of Intensive Care Medicine together with the Mahidol-Oxford Research Unit formed an international team of physicians to revise existent recommendations for sepsis management in resource-limited settings [8]. In this manuscript, we summarize recommendations on sepsis recognition. A detailed description of the guideline team, conflicts of interest, methods, rationales, and references is given in the Online supplement.

Introduction. Acute kidney injury (AKI) is a common occurrence in the intensive care unit (ICU). Studies have looked at outcomes of renal replacement therapy using intermittent haemodialysis (IHD) in ICUs with varying results. Little is known about the outcomes of using IHD in resource-limited settings where continuous renal replacement therapy (CRRT) is limited. We sought to determine outcomes of IHD among critically ill patients admitted to a low-income country ICU.Methods. A retrospective review of patient records was conducted. Patients admitted to the ICU who underwent IHD for AKI were included in the study. Patients’ demographic and clinical characteristics, cause of AKI, laboratory parameters, haemodialysis characteristics, and survival were interpreted and analyzed. Primary outcome was mortality.Results. Of 62 patients, 40 had complete records. Median age of patients was 38.5 years. Etiologic diagnoses associated with AKI included sepsis, malaria, and ARDS. Mortality was 52.5%. APACHE II (OR 4.550; 95% CI 1.2–17.5,p=0.028), mechanical ventilation (OR 13.063; 95% CI 2.3–72,p=0.003), and need for vasopressors (OR 16.8; 95% CI 3.4–82.6,p=0.001) had statistically significant association with mortality.Conclusion. IHD may be a feasible alternative for RRT in critically ill haemodynamically stable patients in low resource settings where CRRT may not be available.

Clinical practice guidelines are systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances. These documents inform and shape patient care around the world. In this Perspective we discuss the importance of diversity on guideline panels, the disproportionately low representation of women on critical care guideline panels, and existing initiatives to increase the representation of women in corporations, universities, and government. We propose five strategies to ensure gender parity within critical care medicine.

Background The intensive care unit (ICU) admits critically ill patients requiring advanced airway, respiratory, cardiac and renal support. Despite the highly-specialized interventions, the mortality and morbidity is still high due to a number of reasons including nosocomial infections, which are the most likely complications in hospitalized patients with the rates being highest among ICU patients. Methods In this cross-sectional study of 111 adult patients admitted to 2 of the ICUs in Uganda, we set out to describe the commonest bacterial infections, their antimicrobial susceptibility patterns and factors associated with development of a nosocomial infection. Results Klebsiella pneumoniae (30%), Acinetobacter species (22%) and Staphylococcus aureus (14%) were the most frequently isolated bacteria. The prevalence of multidrug resistant bacterial species was 58%; 50% Escherichia coli and 33.3% Klebsiella pneumoniae were extended spectrum beta lactamase or AmpC beta lactamase producers and 9.1% Acinetobacter species were extensive drug resistant. Imipenem was the antibiotic with the highest susceptibility rates across most bacterial species. Institution of ventilator support (P 0.003) and severe traumatic brain injury (P 0.035) were highly associated with the development of nosocomial infections. Conclusion Due to the high prevalence of multi drug resistant (MDR) and extensive drug resistant bacterial species, there is a need for development of strong policies on antibiotic stewardship, antimicrobial surveillance and infection control to help guide empirical antibiotic therapy and prevent the spread of MDR bacteria and antibiotic drug resistance. Electronic supplementary material The online version of this article (doi:10.1186/s13104-017-2695-5) contains supplementary material, which is available to authorized users.

BackgroundSub-Saharan Africa has a great burden of critical illness with limited health care resources. We evaluated the feasibility and utility of the modified Sequential Organ Function Assessment (mSOFA) score in assessing morbidity and mortality in the National Referral Hospital's intensive care unit (ICU) for one year.MethodsWe conducted a prospective, observational cohort study on patients above 12years of age admitted to the ICU at Mulago Hospital (Kampala, Uganda). All SOFA scores were determined at admission and at 48h. We modified the SOFA score by replacing the PaO2/FiO2 ratio with SPO2/FiO2. The primary outcome was ICU mortality.ResultsThis ICU cohort of 118 patients had a mean age of 37years and an ICU mortality rate of 46.6%. Non-survivors had higher initial (7.7 SD 3.8 vs. 5.5 SD 3.3; p = 0.007), mean (8.1 SD 3.9 vs 4.7 SD 2.6; p

Recommendations on the management of infections in patients with sepsis and septic shock are mainly derived from studies on bacterial sepsis in high-income settings and are not necessarily applicable elsewhere due to differences in etiology and diagnostic or treatment capacity. In this chapter, we provide recommendations on infection management in resource-limited ICUs, taking into account relevant contextual factors such as the availability, affordability, and feasibility of interventions.

Background Integrated care pathways (ICP) in stroke management are increasingly being implemented to improve outcomes of acute stroke patients. We evaluated the effect of implementing a 72 hour stroke care bundle on early outcomes among patients admitted within seven days post stroke to the national referral hospital in Uganda. Methods In a one year non-randomised controlled study, 127 stroke patients who had ‘usual care’ (control group) were compared to 127 stroke patients who received selected elements from an ICP (intervention group). Patients were consecutively enrolled (controls first, intervention group second) into each group over 5 month periods and followed to 30-days post stroke. Incidence outcomes (mortality and functional ability) were compared using chi square test and adjusted for potential confounders. Kaplan Meier survival estimates and log rank test for comparison were used for time to death analysis for all strokes and by stroke severity categories. Secondary outcomes were in-hospital mortality, median survival time and median length of hospital stay. Results Mortality within 7 days was higher in the intervention group compared to controls (RR 13.1, 95% CI 3.3–52.9). There was no difference in 30-day mortality between the two groups (RR 1.2, 95% CI 0.5–2.6). There was better 30-day survival in patients with severe stroke in the intervention group compared to controls (P = 0.018). The median survival time was 30 days (IQR 29–30 days) in the control group and 30 days (IQR 7–30 days) in the intervention group. In the intervention group, 41patients (32.3%) died in hospital compared to 23 (18.1%) in controls (P < 0.001). The median length of hospital stay was 8 days (IQR 5–12 days) in the controls and 4 days (IQR 2–7 days) in the intervention group. There was no difference in functional outcomes between the groups (RR 0.9, 95% CI 0.4–2.2). Conclusions While implementing elements of a stroke-focused ICP in a Ugandan national referral hospital appeared to have little overall benefit in mortality and functioning, patients with severe stroke may benefit on selected outcomes. More research is needed to better understand how and when stroke protocols should be implemented in sub-Saharan African settings. Trial Registration Pan African Clinical Trials Registry PACTR201510001272347

INTRODUCTION:Providing optimal critical care in developing countries is limited by lack of recognition of critical illness and lack of essential resources. The Modified Early Warning Score (MEWS), based on physiological parameters, is validated in adult medical and surgical patients as a predictor of mortality. The objective of this study performed in Uganda was to determine the prevalence of critical illness on the wards as defined by the MEWS, to evaluate the MEWS as a predictor of death, and to describe additional risk factors for mortality. METHODS:We conducted a prospective observational study at Mulago National Referral Teaching Hospital in Uganda. We included medical and surgical ward patients over 18 years old, excluding patients discharged the day of enrolment, obstetrical patients, and patients who self-discharged prior to study completion. Over a 72-hour study period, we collected demographic and vital signs, and calculated MEWS; at 7-days we measured outcomes. Patients discharged prior to 7 days were assumed to be alive at study completion. Descriptive and inferential statistical analyses were performed. RESULTS:Of 452 patients, the median age was 40.5 (IQR 29-54) years, 53.3% were male, 24.3% were HIV positive, and 45.1% had medical diagnoses. MEWS ranged from 0 to 9, with higher scores representing hemodynamic instability. The median MEWS was 2 [IQR 1-3] and the median length of hospital stay was 9 days [IQR 4-24]. In-hospital mortality at 7-days was 5.5%; 41.4% of patients were discharged and 53.1% remained on the ward. Mortality was independently associated with medical admission (OR: 7.17; 95% CI: 2.064-24.930; p = 0.002) and the MEWS ≥ 5 (OR: 5.82; 95% CI: 2.420-13.987; p

Background Research on cardiac arrest and cardiopulmonary resuscitation (CPR) has considerably increased in recent decades, and international guidelines for resuscitation have been implemented and have undergone several changes. Very little is known about the prevalence and management of in-hospital cardiac arrest in low-resource settings. We therefore sought to determine the prevalence, outcomes and associated factors of adult inpatients with cardiac arrest at a tertiary referral hospital in a low-income country. Methods Upon obtaining institutional approval, we conducted a prospective observational period prevalence study over a 2-month period. We recruited adult inpatients with cardiac arrest in the intensive care unit and emergency wards of Mulago Hospital, Uganda during the study period. We reviewed all files and monitoring charts, and also any postmortem findings. Data were analyzed with Stata 12 and statistical significance was set at p

Background Childbirth is one of the most painful experiences of a woman’s life. Authorities in the fields of obstetrics and anaesthesia encourage use of labour analgesia. Unlike in high-income countries, pain relief in labour in Africa is not a well established service, especially in the low-income countries like Uganda. Little is known about whether parturients would be amenable to labour analgesia. We sought to determine knowledge, attitudes and use of labour analgesia among women attending the antenatal clinic at Mulago National Referral Hospital. Methods Upon obtaining institutional approval, we conducted a cross-sectional descriptive study. Women were requested to complete the researcher-administered survey following informed consent. The study was conducted in the general antenatal clinic at the Mulago National Referral Hospital. Results Of 1293 participants interviewed, only 7 % of the participants had knowledge of labour analgesia. Of the multiparous mothers 87.9 % did not have labour analgesia in their previous deliveries, although 79.2 % of them had delivered in a national referral hospital. The commonest reason for refusal of labour analgesia was to experience natural childbirth. 87.7 % of the participants wanted labour analgesia for their next delivery. Conclusion There is a wide gap between the desire for labour analgesia and its availability. Obstetricians and anaesthesiologists have a role to educate the women, and to provide this much desired service.

Background: Surgery and Anesthesia cause an excessive pro-inflammatory response. Mulago Hospital is faced with staff shortage making post-operative pain management difficult.Interleukin-6 (IL-6) drives inflammatory pain, endothelial cell dysfunction and fibrogenesis. Ketamine is cheap and, readily available. We hypothesized that its attenuation of serum IL-6 was a surrogate for clinical benefit. Materials and methods: Institutional Review Board’s approval was sought and RCT was registered at clinical trials.gov (identifier number: NCT01339065). Consenting patients were randomized to receive pre-incision intravenous ketamine - 0.5mg/kg or 0.9% saline placebo in weighted dosing. Blood samples were collected and laboratory analyzed at baseline, post-operatively in PACU, 24 and 48 hours respectively. Results: We recruited 39 patients of whom 18 were randomized to the ketamine arm and 21 in the placebo arm with follow up at 24 and 48 hours. Serum IL-6 and IL-1β levels were analyzed using ELIZA assay of pre-coated micro wells. Ketamine suppressed serum IL-6 at PACU with reduced increase at 24 hours. There was no reaction in 98% of IL-1β assayed. Conclusion: Low-dose ketamine attenuated early serum IL-6 levels due to surgical response with reduced 24 hour increase, but the difference was not statistically significant and we recommend more studies. Keywords: Ketamine, post-operative inflammation, interleukin 6, interleukin 1- β

Background Prophylactic antibiotics are used to prevent postoperative infections after caesarean section. Studies have suggested that the timing of prophylaxis plays an important role. Over the years, the role of the anaesthesiologist in the administration of prophylactic antibiotics has become prominent. Therefore, there is an increasing need for anaesthesia providers to understand the rationale of antibiotic prophylaxis. We therefore sought to compare the effect of antibiotics prophylaxis within 1 hour before skin incision and after skin incision on the incidence of postoperative infections in patients undergoing caesarean section at Mulago Hospital. Methods We conducted a single-blind randomised clinical trial conducted at Mulago Hospital evaluating 464 patients undergoing emergency caesarean section. Patients were randomly assigned a group number that allocated them to either arm of the study. They received the same prophylactic antibiotic according to their allotment, that is, either within 1 hour before skin incision or after skin incision as per current standards of practice in Mulago Hospital. They were followed up to detect infection up to 10 days postoperatively. The primary outcome was postoperative infection. The data collected were analysed with STATA version 12 using univariate and bivariate analysis. Results The risk of overall postoperative infection was significantly lower when prophylaxis was given within an hour before incision (RR O.77, 95% CI 0.62–0.97). We also found endometritis to be significantly reduced in the pre-incision group (RR 0.62; 95% CI 0.39–0.99; P value 0.036). Conclusions Giving prophylactic antibiotics before skin incision reduces risk of postoperative infection, in particular of endometritis. Trial registration Pan African Clinical Trial Registry PACTR201311000610495. Date of trial registration: 12th August 2013.

Background General and regional anesthesia are the two main techniques used in cesarean section. Regional anesthesia is preferred, but under certain circumstances, such as by patient request and in patients with back deformities, general anesthesia is the only option. Commonly used induction agents include thiopental, ketamine, and propofol, depending on availability and the maternal clinical condition. The objective of this study was to investigate the effects of thiopental and propofol on the neonatal Apgar score and maternal recovery time following emergency cesarean section in order to determine the superior agent for mothers and neonates. Methods This single-blinded randomized clinical trial included 150 ASA I and II patients block-randomized equally between the two study arms. Pregnant women at term scheduled to undergo cesarean section and their neonates were enrolled. The primary outcomes were the Apgar scores through 10-min postpartum, resuscitation requirement, and admission to the neonatal intensive care unit. The secondary outcome was the maternal recovery times. Results At 0 min (umbilical cord clamp time), 43 (57.3%) neonates in the propofol group had an Apgar score

Introduction Mortality from trauma remains a major challenge despite recent substantial improvements in acute trauma care. In trauma care patient resuscitation to correct hypotension from volume loss still majorly relies on use of physiological parameters such as blood pressure, pulse rate, respiratory rate, urine output and oxygen saturation. In resource limited settings these methods may not be sufficient to detect occult tissue hypoxia and the accompanying metabolic derangements. Methods A prospective observational study carried out at a level I urban Trauma centre; Accident and Emergency unit. Major trauma patients were consecutively recruited into the study. Venous blood samples were drawn for analysis of serum electrolytes, serum PH and anion gap. The venous blood gas findings were correlated with patients’ clinical outcome at two weeks. Ethical approval was obtained. Results Ninety three major trauma patients were recruited, patients’ age ranged from 12 months to 50 years. Forty nine patients (53%) were acidotic (PH less than 7.32), 39 patients (42%) had low bicarbonate (bicarbonate level less than 21 mmol), 54 patients (58%) had high corrected anion gap (anion gap corrected of 16 or more). Fourteen patients (15%) developed secondary organ failure and 32 (34%) patients died. Conclusion Metabolic acidosis is common among major trauma patients, its severity may be related to delay in initiating care. Acid base derangements were predictors of mortality among major trauma patients in this resource limited setting.

Surgery and perioperative care have been neglected in the arena of global health despite evidence of cost-effectiveness and the growing, substantial burden of surgical conditions. Various approaches to address the surgical disease crisis have been reported. This article describes the strategy of Global Partners in Anesthesia and Surgery (GPAS), an academically based, capacity-building collaboration between North American and Ugandan teaching institutions.The collaboration's projects shift away from the trainee exchange, equipment donation, and clinical service delivery models. Instead, it focuses on three locally identified objectives to improve surgical and perioperative care capacity in Uganda: workforce expansion, research, collaboration.Recruitment programs from 2007 to 2011 helped increase the number of surgery and anesthesia trainees at Mulago Hospital (Kampala, Uganda) from 20 to 40 and 2 to 19, respectively. All sponsored trainees successfully graduated and remained in the region. Postgraduate academic positions were created and filled to promote workforce retention. A local research agenda was developed, more than 15 collaborative, peer-reviewed papers have been published, and the first competitive research grant for a principal investigator in the Department of Surgery at Mulago was obtained. A local projects coordinator position and an annual conference were created and jointly funded by partnering international efforts to promote collaboration.Sub-Saharan Africa has profound unmet needs in surgery and perioperative care. This academically based model helped increase recruitment of trainees, expanded local research, and strengthened stakeholder collaboration in Uganda. Further analysis is underway to determine the impact on surgical disease burden and other important outcome measures.

Purpose To provide clinicians practicing in resource-limited settings with a framework to improve the diagnosis and treatment of pediatric and adult patients with sepsis. Methods The medical literature on sepsis management was reviewed. Specific attention was paid to identify clinical evidence on sepsis management from resource-limited settings. Results Recommendations are grouped into acute and post-acute interventions. Acute interventions include liberal fluid resuscitation to achieve adequate tissue perfusion, normal heart rate and arterial blood pressure, use of epinephrine or dopamine for inadequate tissue perfusion despite fluid resuscitation, frequent measurement of arterial blood pressure in hemodynamically unstable patients, administration of hydrocortisone or prednisolone to patients requiring catecholamines, oxygen administration to achieve an oxygen saturation >90%, semi-recumbent and/or lateral position, non-invasive ventilation for increased work of breathing or hypoxemia despite oxygen therapy, timely administration of adequate antimicrobials, thorough clinical investigation for infectious source identification, fluid/tissue sampling and microbiological work-up, removal, drainage or debridement of the infectious source. Post-acute interventions include regular re-assessment of antimicrobial therapy, administration of antimicrobials for an adequate but not prolonged duration, avoidance of hypoglycemia, pharmacological or mechanical deep vein thrombosis prophylaxis, resumption of oral food intake after resuscitation and regaining of consciousness, careful use of opioids and sedatives, early mobilization, and active weaning of invasive support. Specific considerations for malaria, puerperal sepsis and HIV/AIDS patients with sepsis are included. Conclusion Only scarce evidence exists for the management of pediatric and adult sepsis in resource-limited settings. The presented recommendations may help to improve sepsis management in middle- and low-income countries. Electronic supplementary material The online version of this article (doi:10.1007/s00134-012-2468-5) contains supplementary material, which is available to authorized users.

Background Primary health care delivery in the developing world faces many challenges. Priority setting favours HIV, TB and malaria interventions. Little is known about the challenges faced in this setting with regard to critical care medicine. The aim of this study was to analyse and categorise the diagnosis and outcomes of 1,774 patients admitted to a hospital intensive care unit (ICU) in a low-income country over a 7-year period. We also assessed the country’s ICU bed capacity and described the challenges faced in dealing with critically ill patients in this setting. Findings A retrospective audit was conducted in a general ICU in a university hospital in Uganda. Demographic data, admission diagnosis, and ICU length of stay were recorded for the 1,774 patients who presented to the ICU in the period January 2003 to December 2009. Their mean age was 35.5 years. Males accounted for 56.5% of the study population; 92.8% were indigenous, and 42.9% were referrals from upcountry units. The average mortality rate over the study period was 40.1% (n = 715). The highest mortality rate (44%) was recorded in 2004 and the lowest (33.2%) in 2005. Children accounted for 11.6% of admissions (40.1% mortality). Sepsis, ARDS, traumatic brain injuries and HIV related conditions were the most frequent admission diagnoses. A telephonic survey determined that there are 33 adult ICU beds in the whole country. Conclusions Mortality was 40.1%, with sepsis, head injury, acute lung injury and HIV/AIDS the most common admission diagnoses. The country has a very low ICU bed capacity. Prioritising infectious diseases poses a challenge to ensuring that critical care is an essential part of the health care package in Uganda.

Background: In developing countries, post-operative pain remains underestimated and undertreated due to economic constraints, lack of awareness and limited resources. In contrast, ketamine is an effective, readily available, easy to use and inexpensive drug frequently used in poor settings. Objectives: The aim of this study was to explore the overall reduction in the medication treatment cost of acute post-operative pain by adding intra-operative low-dose ketamine to traditional intravenous morphine for surgery in a low-income country. Methods: A double blind randomized controlled trial with placebo-controlled parallel group was performed in Mulago National Hospital (Uganda). Consenting adults scheduled for elective surgery were randomized into two study arms: Group K received ketamine 0.15mg/kg bolus at induction and a continuous infusion of 0.12 mg/kg/hour till start of skin closure; Group C (control) received normal saline. Both groups received Morphine 0.1 mg/kg IV at debulking. The total medication cost was registered. NRS pain scores and other measurements such vital signs and incidence of major and minor side effects were also recorded. Results: A total of 46 patients were included. Patients’ baseline characteristics were comparable in both groups. No statistically significant difference was found between the groups concerning the overall medication cost of post-operative pain management. Pain scores, patients’ satisfaction in the first 24 hours after surgery and hospital length of stay were similar in both groups. Conclusion: Our results do not support the utilization of intra-operative low dose ketamine as a cost-saving post-operative pain treatment strategy for all types of surgery in low-resource settings. Keywords: Post-operative pain management, ketamine, low-income country, RCT.

Background Acute kidney injury (AKI) is a common complication of sepsis. We determined the prevalence of AKI among adult patients with sepsis on the medical wards in a low-income country and described their clinical pattern and outcomes at discharge. Methods We conducted a cross-sectional study of sepsis-related AKI on the adult medical wards of Mulago National Referral Hospital between January and April 2013. All patients meeting the American College of Chest Physicians (ACP) sepsis criteria were recruited. Demographic, clinical, laboratory and ultrasonography data were recorded and all patients with AKI were followed up to a maximum of 2 weeks. Proportional analysis was carried out and odds ratios with 95% confidence intervals were calculated in the bivariate analysis. Results Of 387 patients recruited, 217 (55.6%) were male and the average age was 37 years (range18–90 years). The prevalence of sepsis-related AKI was 16.3%. Age >59 years (p = 0.023), a postural drop in systolic blood pressure of >9 mmHg (p = 0.015) and a white blood cell count >12,000 cells/mL (p = 0.003) were significantly associated with AKI. In-hospital mortality among patients with AKI was 21% (13/63). 59% (20/49) of patients who were discharged alive or were still on the wards after 2 weeks had persistent kidney injury. Acute Kidney Injury Network (AKIN) Stage 3 was significantly associated with persistence of kidney injury (p = 0.001). None of the patients requiring dialysis or ICU care received either because of limited access. Conclusions The prevalence, morbidity and mortality due to AKI among sepsis patients in Uganda is very high and limited access to dialysis and ICU care is a major factor in poor outcomes for these patients.