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Introduction: Postoperative hypoxemic respiratory failure (PHRF) is a significant cause of morbidity and mortality in emergency surgery and anesthesia [1]. Identifying patients at risk for PHRF is important for better patient outcomes. There is however little data describing the burden of PHRF and its risk factors in low-resource- setting such as Uganda. This study aimed to determine the incidence, risk factors, and outcomes of postoperative hypoxemic respiratory failure following emergency surgical procedures at the causality theatre, Mulago National Referral Hospital (MNRH). Methods:Patients who underwent emergency surgery at the causality theatre of MNRH between March and April 2022 were assessed for PHRF within the first 5 days of postoperative. Background data were collected using questionnaires and medical records to assess risk factors. The patients were then followed up for 28 days post-operative to assess mortality. Analysis was done using Stata version 15 and Poisson regression was done to assess the risk factors for PHRF. Results: Out of 389 participants recruited, 345 participants had their data analyzed. 78.3% were male and the mean age of the participants was 39.0 years. 14.5% developed PHRF within the first five postoperative days which was the overall incidence of PHRF. At multivariate analysis, four factors were significantly associated with the incidence of PHRF, that is, ASA score > 2 with a ninefold risk (8.58, 3.75-19.62, p Conclusions: PHRF is common within the first 5 days of post-operative with a high incidence rate of 14.5% following emergency surgery. Close monitoring of emergency surgical patients especially those with a smoking history, high blood loss, ASA score >2, or using a nasogastric tube preoperatively to allow early recognition and treatment of PHRF may reduce the risk of death.

Background: Precision medicine focuses on the identification of therapeutic strategies that are effective for a group of patients based on similar unifying characteristics. The recent success of precision medicine in non–critical care settings has resulted from the confluence of large clinical and biospecimen repositories, innovative bioinformatics, and novel trial designs. Similar advances for precision medicine in sepsis and in the acute respiratory distress syndrome (ARDS) are possible but will require further investigation and significant investment in infrastructure. Methods: This project was funded by the American Thoracic Society Board of Directors. A multidisciplinary and diverse working group reviewed the available literature, established a conceptual framework, and iteratively developed recommendations for the Precision Medicine Research Agenda for Sepsis and ARDS. Results: The following six priority recommendations were developed by the working group: 1) the creation of large richly phenotyped and harmonized knowledge networks of clinical, imaging, and multianalyte molecular data for sepsis and ARDS; 2) the implementation of novel trial designs, including adaptive designs, and embedding trial procedures in the electronic health record; 3) continued innovation in the data science and engineering methods required to identify heterogeneity of treatment effect; 4) further development of the tools necessary for the real-time application of precision medicine approaches; 5) work to ensure that precision medicine strategies are applicable and available to a broad range of patients varying across differing racial, ethnic, socioeconomic, and demographic groups; and 6) the securement and maintenance of adequate and sustainable funding for precision medicine efforts. Conclusions: Precision medicine approaches that incorporate variability in genomic, biologic, and environmental factors may provide a path forward for better individualizing the delivery of therapies and improving care for patients with sepsis and ARDS.

Severe Traumatic brain injury (STBI) is a leading cause of morbidity and mortality among young individuals worldwide with worse outcomes being registered in low-income countries. Brain trauma foundation recommends the management of patients with TBI in the intensive care unit (ICU) to prevent secondary brain injury for improved outcome. However, Uganda being a low-income country, still grapples with the availability of ICU resources and space. Information regarding burden, predictors and short-term outcomes of ICU patients with TBI in Uganda has never been reconnoitered. A multicenter prospective observational cohort was conducted between 2013 to 2015 at four Ugandan ICUs. During the study period, we consecutively enrolled 387 critically ill, adult patients with TBI to determine the burden, predictors and short term outcomes in these patients. . Baseline demographics, clinical and treatment parameters were recorded and followed till discharge from ICU or death. Of 387 patients enrolled in the study, 277 (71.6%) had moderate TBI, while 113 (29.2%) patients had STBI. The highest burden of TBI was recorded among patients assaulted through mob violence, recorded at 17/21 (81.0%), as shown in table 5. The overall mortality was at 34.4% (95/277) among patients with moderate or severe TBI, and 46.9% (53/113) among patients with STBI alone. Mortality was relatively higher among patients brought by the police, and those brought in at night. Multivariate analysis showed patient intubation, lack of antibiotic use, failure to transfuse, tracheostomy tube not inserted, and being involved in RTA or sustaining a fall were significantly associated with mortality among patients with TBI. We found a high burden of TBI and mortality among ICU patients. Despite limited resources in the local setting, inexpensive and locally available measures can reduce on the length of patient’s stay in the ICU and eventually decrease on the mortality. Improvement in prehospital as well as early trauma and airway care, antibiotic use, blood transfusion plus public health safety measures may reduce on the burden of TBI as well as improve outcomes.

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.

BackgroundSeveral 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. DesignWe conducted a randomized open label Phase II clinical trial from October -December 2020.MethodsPatients 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 400mg twice a day for the first day followed by 200mg twice daily for the next 4 days plus standard of care (SOC) treatment or SOC treatment alone. SARS COV-2 viral load 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.ResultsOf 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.ConclusionOur results show that HCQ 400mg twice a day for the first day followed by 200mg twice daily for the next 4 days was safe but not associated with reduction in viral clearance or symptom resolution. Trial registration: NCT04860284

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.

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.

Background. Hands of healthcare workers (HCWs) are vehicles for pathogens responsible for healthcare-associated infections (HAIs). Following the identification of Gram-negative organisms (GNOs) in all cases of HAIs in the cardiac intensive care unit (ICU), we sought to determine the burden of hand colonization with GNOs among healthcare workers who access the cardiac ICU. Methods. We retrospectively reviewed results from surveillance cultures of fingertip imprints of HCWs who access the cardiac ICU at the Uganda Heart Institute. We collected data on staff category, isolates, and susceptibility to antibiotics. We analyzed the data using Microsoft Excel, and the results are summarized in proportions and percentages and presented in charts and tables. Results. Fifty-six healthcare workers participated in the surveillance. 21 were ICU clinicians, 21 non-ICU clinicians, and 14 nonclinicians. GNOs were cultured in 19 (33.9%) HCWs, in which 8/19 (42.1%) were non-ICU clinicians, 6/19 (31.2%) ICU clinicians, and 5/19 (26.3%) nonclinicians. 32 isolates were identified, of which 47%, 28%, and 25% were cultured from non-ICU clinicians, nonclinicians, and ICU clinicians, respectively. Predominant isolates were Acinetobacter (34%), Citrobacter (21.9%), and Pseudomonas (21.9%). Antimicrobial resistance ranged from 4% to 90%. 9/28 (32.1%) isolates, predominantly Acinetobacter species (spp), were carbapenem resistant. 8/28 (28.6%) isolates, predominantly Citrobacter spp, were multidrug resistant. Resistance to ciprofloxacin and cefepime was low at 3.6% and 4.4%, respectively. Conclusion. Gram-negative organisms, predominantly Acinetobacter, Citrobacter, and Pseudomonas spp, were prevalent on the hands of HCWs who access the cardiac ICU irrespective of the staff category. Antimicrobial resistance was high, with multidrug resistance and carbapenem resistance common among Citrobacter spp and Acinetobacter spp, respectively. Resistance to cefepime and ciprofloxacin was low.

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.

In this chapter, we summarize recommendations on sepsis recognition, identification of the underlying infection and causative microbiological pathogen, as well as recognition of septic shock in resource-limited settings. Early recognition of sepsis is based on the quick Sequential (Sepsis-related) Organ Failure Assessment (qSOFA): respiratory rate ≥22 bpm, systolic blood pressure ≤100 mmHg, and any acute change in mental state. For patients with severe malaria and severe dengue, more disease-specific criteria are of additional value. Identifying the cause and source of infection is important for the choice of treatment, to which knowledge of the local epidemiology, physical examination, and, depending on their availability, laboratory testing and imaging can contribute. If feasible, microbiological cultures before antimicrobial therapy, microscopy, and Gram staining of secretions sampled from the suspected source of infection should be performed. Empirical antibiotic therapy should be informed considering local antimicrobial resistance patterns, and if available follow-on antibiotic therapy should be guided by the antibiotic susceptibility of cultured bacteria. Malaria is diagnosed by rapid diagnostic test or light microscopy of a peripheral blood smear. Antigen or antibody tests are available for specific virus infections such as dengue, influenza, or Ebola virus disease. In immunocompromised patients, coinfection with tuberculosis should be suspected. For the diagnosis of septic shock, clinical indicators of systemic tissue hypoperfusion should be assessed. It is insufficient to rely solely on the presence of arterial hypotension, as arterial hypotension can be a late event. Plasma lactate is an important indicator of tissue hypoperfusion with strong prognostic significance.

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.

Background: Intra-abdominal hypertension (IAH) is sustained increase in intra-abdominal pressure (IAP) ≥12 mmHg in adults and ≥10 mmHg in children. IAH has been noted to be associated with increased morbidity and mortality among critically ill patients. Measurement of IAP is common among at risk patients in the developed world. However, it has not received due attention in the majority of intensive care units (ICUs) in low-income countries, Uganda being one of these. This is evidenced by paucity of data and lack of protocols from the Ugandan Ministry of Health. This multi-center study was thus conducted to assess the prevalence, incidence and mortality associated with IAH among patients admitted to Ugandan ICUs.Methods:A multi-center prospective cohort study was conducted from September 2017 to February 2018 at three ICUs in Uganda. We consecutively enrolled 126 patients into the study. IAP was measured using the Harrahil manometer technique. Categorical variables were analyzed using the Chi square test and continuous variables analyzed using the t-test and Man Whitney test. The prevalence and incidence were determined using proportions and mortality was determined using survival analysis.Results:The median age was 33 years (26-48.5) for the patients without IAH and 42 years (29-55) for those with IAH. The majority of the patients were male and 9.6% of the patients were below 18 years. The prevalence of IAH was 62.7 (CI 54.1-71.3), whereas the 24 hour and 72 hour incidence of IAH was 9.3% (CI 1.3-17.2) and 14.3 % (CI 4.1-24.4), respectively. Mortality was higher in patients with IAH compared to those without (p-value 0.003 and 0.028, mean and maximum IAP, respectively). Conclusion:We found a high prevalence and incidence of IAH among critically ill patients, associated with a high mortality. Routine screening for IAH can preempt management strategies to mitigate this.