Hemoadsorption Therapy for Calcium Channel Blocker Overdose: A Case Report.

BACKGROUND: Modern resin hemoadsorption/hemoperfusion for calcium channel blocker overdose is yet to be reported. The characteristics of calcium channel blockers make them unamenable to removal by hemodiafiltration or charcoal hemoperfusion; however, elimination, using styrene bead adsorption in an ex vivo model, has been demonstrated. Its clinical use is described. CASE REPORT: A man in his 20s was admitted with shock into the Intensive Care Unit (ICU) after an overdose of amlodipine and risperidone. Resuscitation and supportive care were administered, but hypotension did not resolve despite the administration of intravenous fluids, infusions of calcium, adrenaline, and hyperinsulinemic-euglycemic therapy. Methylene blue was then administered to maintain the mean arterial pressures. However, the hemodynamic effect did not allow the weaning of the adrenaline. Drug clearance using hemoadsorption/hemoperfusion was attempted using a styrene resin filter (Jafron HA230; Jafron Biomedical Co., Ltd., Guangdong, China). During the two hemoperfusion sessions (6 h duration each, and 18 h apart) the patient had successfully weaned off all supportive measures, with lactate levels returning to normal and was later discharged home. At the end of each session, significant amlodipine concentrations were detected in blood aspirated from both filters, suggesting enhanced clearance. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Our case illustrates a temporal relationship between resin hemoperfusion therapy, resolution of hemodynamic instability, and shock without proving causation. Significant amlodipine elimination was suggested by high concentrations found in blood from the filter. At the same time, shock resolution after initiation of hemoperfusion occurred in less than one elimination half-life of amlodipine.

Prolonged vs Intermittent Infusions of ß-Lactam Antibiotics in Adults With Sepsis or Septic Shock: A Systematic Review and Meta-Analysis.

Importance: There is uncertainty about whether prolonged infusions of ß-lactam antibiotics improve clinically important outcomes in critically ill adults with sepsis or septic shock. Objective: To determine whether prolonged ß-lactam antibiotic infusions are associated with a reduced risk of death in critically ill adults with sepsis or septic shock compared with intermittent infusions. Data Sources: The primary search was conducted with MEDLINE (via PubMed), CINAHL, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov from inception to May 2, 2024. Study Selection: Randomized clinical trials comparing prolonged (continuous or extended) and intermittent infusions of ß-lactam antibiotics in critically ill adults with sepsis or septic shock. Data Extraction and Synthesis: Data extraction and risk of bias were assessed independently by 2 reviewers. Certainty of evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation approach. A bayesian framework was used as the primary analysis approach and a frequentist framework as the secondary approach. Main Outcomes and Measures: The primary outcome was all-cause 90-day mortality. Secondary outcomes included intensive care unit (ICU) mortality and clinical cure. Results: From 18 eligible randomized clinical trials that included 9108 critically ill adults with sepsis or septic shock (median age, 54 years; IQR, 48-57; 5961 men [65%]), 17 trials (9014 participants) contributed data to the primary outcome. The pooled estimated risk ratio for all-cause 90-day mortality for prolonged infusions of ß-lactam antibiotics compared with intermittent infusions was 0.86 (95% credible interval, 0.72-0.98; I2 = 21.5%; high certainty), with a 99.1% posterior probability that prolonged infusions were associated with lower 90-day mortality. Prolonged infusion of ß-lactam antibiotics was associated with a reduced risk of intensive care unit mortality (risk ratio, 0.84; 95% credible interval, 0.70-0.97; high certainty) and an increase in clinical cure (risk ratio, 1.16; 95% credible interval, 1.07-1.31; moderate certainty). Conclusions and Relevance: Among adults in the intensive care unit who had sepsis or septic shock, the use of prolonged ß-lactam antibiotic infusions was associated with a reduced risk of 90-day mortality compared with intermittent infusions. The current evidence presents a high degree of certainty for clinicians to consider prolonged infusions as a standard of care in the management of sepsis and septic shock. Trial Registration: PROSPERO Identifier: CRD42023399434.

Hemoperfusion for Clinically Suspected Organophosphate and Carbamate Poisoning in Critically Ill Patients: A Randomized Trial.

INTRODUCTION: Organophosphate poisoning occurs frequently, and despite treatment, increased severity and intensive care unit (ICU) admissions have been observed. We hypothesized that early hemoperfusion/hemadsorption (HA) therapy would change the clinical course of the disease. METHODS: We performed a prospective, open, randomized controlled study at an academic ICU. Adult patients referred for an acute cholinergic toxidrome were screened. Patients meeting inclusion and exclusion criteria were randomized to standard of care (SoC) or HA therapy plus SoC, which included 2 6-h cycles of HA 12 h apart beginning within the first 24 h of ICU admission. The primary outcome was a comparison of ICU length of stay (LOS). RESULTS: There were no significant baseline differences between the groups. The median ICU LOS was 6.5 days (IQR 4.5-10) in the HA group compared to 8 days (IQR 3.5-17) for the control group, p = 0.58. Among patients with an excess ICU LOS ≥7 days, the median ICU LOS was significantly shorter for the HA group, 10 days (IQR 8-12) compared to 17 days (IQR 14-22) for the control group, p = 0.001, resulting in a cost saving of EUR 7308 per patient. Duration (8 days vs. 13.5 days) and cumulative dosage (316 mg vs. 887 mg) of atropine among patients with excess ICU LOS were significantly lower in the HA group compared to the SoC group, respectively. A similar reduction in the duration of mechanical ventilation (HA = 6 days vs. SoC = 15 days, p = 0.001) was found. The combination of day 28 mortality and severe complications was lower in the HA group (10%, n = 2/20) compared to the SoC group (42%, 14/33) p = 0.01. CONCLUSION: HA therapy resulted in significant cost savings driven by a reduced LOS among patients with excess ICU LOS ≥7 days. This therapy was also associated with a significant reduction in the combination of day 28 mortality and severe complications including cardiac arrest, organ dysfunction, reintubation, and tracheostomy.

Factor Xa Levels in Patients Receiving Prophylactic Enoxaparin Sodium in the Intensive Care Unit of an Academic Hospital.

Background: The aim of this study was to determine the anti-factor Xa levels in patients receiving enoxaparin sodium for venous thromboembolism prophylaxis in the intensive care unit (ICU). Patients and methods: Using a cross-sectional study methodology, 73 ICU patients receiving 40 mg enoxaparin sodium daily were enrolled in this study. Anti-factor Xa levels were measured following the second dose. Prophylactic and subprophylactic groups of patients were compared for age, sex, weight, body mass index, total bilirubin, serum albumin, and APACHE II score. Results: Anti-factor Xa levels were prophylactic (0.2-0.6 IU/mL) in 44 (60.3%) patients and subprophylactic (<0.2 IU/mL) in 29 (39.7%) patients. The mean (SD) actual delivered dose of enoxaparin per kilogram body weight was significantly higher, at 0.59 (0.11) mg/kg in the prophylactic group compared to 0.53 (0.13) mg/kg in the subprophylactic group (p = 0.043). The subprophylactic group had significantly lower serum albumin levels compared to the prophylactic group. The total bilirubin levels were not found to be significantly different between the two groups (p = 0.110). Conclusion: A fixed prophylactic 40 mg dose of enoxaparin was associated with a high proportion of subprophylactic anti-factor Xa levels. Weight-based dose and serum albumin level were independent predictors of achieving the prophylactic target range. How to cite this article: Baloo MM, Scribante J, Perrie H, Calleemalay D, Omar S. Factor Xa Levels in Patients Receiving Prophylactic Enoxaparin Sodium in the Intensive Care Unit of an Academic Hospital. Indian J Crit Care Med 2021;25(8):917-919.

The Clinical Utility of Noninvasive Pulse Co-oximetry Hemoglobin Measurements in Dark-Skinned Critically Ill Patients.

BACKGROUND: The primary objective of this study was to assess the clinical usefulness of a point-of-care device which measures hemoglobin noninvasively (SpHb) in a group of critically ill participants with dark skin pigmentation. METHODS: One hundred forty-six adult and pediatric participants from a multidisciplinary intensive care unit had intermittent readings of noninvasive hemoglobin measurements performed at a minimum of 4 hourly intervals. A total of 371 readings were analyzed. Concurrent blood samples were taken to assess hemoglobin levels using point-of-care blood gas analyzer, as well as sent to a central laboratory where hemoglobin was measured using the sodium lauryl sulfate method. Bland-Altman plots were constructed to assess the agreement between results from the 2 point-of-care devices with the reference standard (laboratory hemoglobin). RESULTS: SpHb exhibited significant bias when compared to laboratory hemoglobin, while blood gas hemoglobin did not. Mean bias for SpHb was +1.64 with limits of agreement of -1.03 to 4.31 compared to blood gas hemoglobin which showed a bias of 0.26 and limits of agreement of -0.84 to 1.37. The magnitude of the bias for SpHb increased with increasing mean hemoglobin levels. Of all the additional study variables assessed for effect on the bias, only Acute Physiology and Chronic Health Evaluation II score in adult patients (P < .0001) and mean arterial blood pressure (P = .001) had an effect. Skin pigmentation did not have any effect on the magnitude of bias. CONCLUSIONS: Noninvasive Hemoglobin measurement is a promising tool in dark-skinned critically ill patients with low hemoglobin levels, but requires further refinements for it to have clinical usefulness.

Changes in B-type Natriuretic Peptide and Related Hemodynamic Parameters Following a Fluid Challenge in Critically Ill Patients with Severe Sepsis or Septic Shock.

CONTEXT: Severe sepsis or septic shock. AIMS: The aim of this study is to examine the effect of a fluid challenge on the B-type natriuretic peptide (BNP) and the hemodynamic state. SETTINGS AND DESIGN: This observational study was conducted in an intensivist-led academic, mixed medical-surgical Intensive Care Unit. SUBJECTS AND METHODS: Focused transthoracic echocardiogram, plasma BNP, and hemodynamic measurements were recorded at baseline and following a 500 ml fluid challenge in thirty patients. Independent predictors of the percentage (%) change in stroke volume (SV) were sought. Next, these independent predictors were assessed for a relationship with the percentage change in BNP. STATISTICAL ANALYSIS USED: Multiple linear regressions, Wilcoxon rank-sum test, t-test, and Pearson's correlation were used. Data analysis was carried out using SAS. The 5% significance level was used. RESULTS: Using a multiple regression models, the percentage increase in SV was independently predicted by the percentage increase in mean arterial pressure, left ventricular end-diastolic volume/dimension (LVEDV/LVEDd), ejection fraction, and a decrease in Acute Physiology and Chronic Health Evaluation II score (P < 0.0001). Preload, measured using LVEDV1 (before the fluid challenge) was significantly larger in the fluid nonresponders (%SV increase <15%) vs. the responders (%SV increase ≥15%). Finally, the percentage change in BNP was positively correlated with left ventricular size at end diastole LVEDd, r = 0.4, P < 0.035). CONCLUSIONS: An increase in BNP soon after a fluid challenge may have some predictive utility of a large LVEDd, which in turn can be used to independently predict the SV response to a fluid challenge.

A review of adult resuscitative fluid purchasing and usage trends at an academic tertiary hospital in Johannesburg.

BACKGROUND: Intravenous fluid administration is a vital component in the resuscitation of critically ill patients. In recent years, there have been many studies to help guide which fluids should be used for resuscitation. Currently, it appears that the international trend is away from the use of colloids and unbalanced crystalloids and towards the use of balanced crystalloids. The aim of our study was to determine whether evolving international evidence has impacted resuscitative fluid practices in the Emergency Department (ED) and the Intensive Care Unit (ICU) in a tertiary hospital in South Africa. METHODS: The study design was two-fold: a cross-sectional physician survey and a retrospective longitudinal observational study of the pharmacy fluid purchase records from the combined ED and ICU. RESULTS: Cross-sectional survey: in 2020 a doctor was 8.3 times more likely to choose a balanced crystalloid for resuscitation regardless of the clinical scenario over any other fluid (CI: 5.0-13.8). 55% of doctors surveyed agreed that their resuscitation fluid of choice had changed for a variety of reasons with the most popular reason cited as post-graduate education. Retrospective longitudinal observational study: throughout the study period, balanced crystalloids were the majority fluid purchased, although in ED lactated Ringers was the preferred balanced crystalloid and in ICU PlasmaLyte was preferred. Minimal colloids were purchased over the study period in declining amounts. CONCLUSIONS: Doctors working in a tertiary hospital in South Africa are following the trend of current evidence by using a balanced crystalloid as their resuscitation fluid of choice.

Vitamin D status and COVID-19 severity.

Background: Age, body mass index (BMI) and pre-existing comorbidities are known risk factors of severe coronavirus disease 2019 (COVID-19). In this study we explore the relationship between vitamin D status and COVID-19 severity. Methods: We conducted a prospective, cross-sectional descriptive study. We enrolled 100 COVID-19 positive patients admitted to a tertiary level hospital in Johannesburg, South Africa. Fifty had symptomatic disease (COVID-19 pneumonia) and 50 who were asymptomatic (incidental diagnosis). Following written informed consent, patients were interviewed regarding age, gender and sunlight exposure during the past week, disease severity, BMI, calcium, albumin, magnesium and alkaline phosphatase levels. Finally, blood was collected for vitamin D measurement. Results: We found an 82% prevalence rate of vitamin D deficiency or insufficiency among COVID-19 patients. Vitamin D levels were lower in the symptomatic group (18.1 ng/mL ± 8.1 ng/mL) than the asymptomatic group (25.9 ng/mL ± 7.1 ng/mL) with a p-value of 0.000. The relative risk of symptomatic COVID-19 was 2.5-fold higher among vitamin D deficient patients than vitamin D non-deficient patients (confidence interval [CI]: 1.14-3.26). Additional predictors of symptomatic disease were older age, hypocalcaemia and hypoalbuminaemia. Using multiple regression, the only independent predictors of COVID-19 severity were age and vitamin D levels. The patients exposed to less sunlight had a 2.39-fold increased risk for symptomatic disease compared to those with more sunlight exposure (CI: 1.32-4.33). Conclusion: We found a high prevalence of vitamin D deficiency and insufficiency among patients admitted to hospital with COVID-19 and an increased risk for symptomatic disease in vitamin D deficient patients.

Oxygen efficient respiratory Aid (OxEraTM) device: A safety study.

Background: Severe Coronavirus Disease 2019 (COVID-19) can develop pneumonia with severe complications. The Oxygen Efficient Respiratory Aid (OxEraTM) device has been granted SAPHRA approval for emergency COVID-19 pandemic use. The device has the potential to be used widely in the healthcare sector due to its efficient oxygen supply and adjustable wall positive expiratory pressure (PEP). Objectives: We assessed whether the OxEraTM device was safe to use in a healthy adult volunteer population. Our primary objective was to ensure there was no asphyxiation, as assessed by changes observed from baseline End Tidal Carbon Dioxide (ETCO2) exceeding 6.3 mmHg and above the 45 mmHg threshold. We also monitored changes in vital organ signs and assessed the pain and comfort of the participant at various intervals with changes in PEPs. Methods: This was an experimental safety study of the OxEraTM Device on 30 healthy participants at the ICU training centre of Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa. Each participant had basic vital-signs, ETCO2, and Oxygen saturation percentages (SpO2%) taken at baseline until the end of 2 h. In the first 20 min, the PEP was increased by 5 cmH20 until 20 min, then continued for the rest of the time on a PEP of 5 cmH20. At each interval, vital signs, subjective comfort, pain, and visual scores were measured. Results: Thirty healthy participants were enrolled. There was no significant difference in ETCO2 from baseline until 2 h. No participant experienced an increase in measured ETCO2 greater than 45 mmHg and no increase in ETCO2 from baseline was greater than 6.3 mmHg. The median increase in ETCO2 over the study period was 2 mmHg. There were no significant changes in respiratory rate and blood pressure. The heart rate decreased significantly (73-68 bpm). The VAS and comfort score had a significant increase over the 2 h from baseline of 0-2 at maximum; however, the PAS scores showed no significant increase. Conclusion: Overall the OxEraTM device achieved the safety endpoints set out. There was no sign of asphyxiation and there were appropriate physiological responses to changes in PEP once applied. The comfort of the mask did worsen over the 2 h; however, the scores were minimally worse on PEP application but improved once-off PEP. No adverse event was recorded at all.

A retrospective comparison of the burden of organophosphate poisoning to an Intensive Care Unit in Soweto over two separate periods.

INTRODUCTION: Organophosphate poisoning (OPP) is a major health-care burden in South Africa. Recently, we have observed that patients admitted to our Intensive Care Unit (ICU) with OPP have followed a more complicated course in comparison to previous years. OBJECTIVES: To describe the differences in the clinical course and costs of patients with OPP between two time periods, namely 2012 and 2017. METHODS: Retrospective comparison of patients admitted to the Intensive Care Unit (ICU) of Chris Hani Baragwanath Academic Hospital between January 2012 to December 2012 and January 2017 to December 2017. RESULTS: Forty-one patients were found in the database. Patients from our 2017 cohort showed a significantly longer total median (IQR) length of stay 8 (4-17) days vs. 2 (2-3) days, p = 0.000, duration of antidote therapy 5 (3-10) days vs. 2 (2-3) days, p = 0.004 and duration of ventilation 4 (2-11) days vs 1 (1-2) day, p = 0.003. Patients presenting in 2017 were more likely to be admitted to ICU, odds ratio 5.6 (CI 1.2-26). There was a 31- fold increase in ICU costs between 2012 and 2017. CONCLUSION: Based on our experience, the clinical course of OPP requiring ICU admission has evolved into a condition with a longer length of stay, duration of antidote therapy, ventilatory support, increased risk of complications and additional costs.

Prevalence and Trajectory of COVID-19-Associated Hypercoagulability Using Serial Thromboelastography in a South African Population.

INTRODUCTION: The coagulation abnormalities resulting from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been attributed to inflammation and subsequent cytokine storm. Thromboelastography (TEG) is a point-of-care test used to assess clot formation and degradation in whole blood and is an indicator of the overall real-time coagulopathic state of the patient. METHODS: A single-centre, prospective, observational cohort study was conducted in South Africa, analysing the coagulation patterns of 41 patients with hypoxia related to SARS-CoV-2 using serial thromboelastography (TEG) on admission, after 48 hours, and at resolution of hypoxia/day 10. Results: Two-thirds (n = 26) were women. The median age was 61 (IQR 50-67), and the majority (88%) were Black patients. Almost half (22) of the patients were critically ill and ventilated, with median SOFA and SAPS2 scores of 3 and 22 (IQR2-4 and 18-30), respectively. The prevalence of hypercoagulability was 0.54 (95% CI 0.46-0.62), whilst 29/41 (0.71, CI 0.64-0.78)) met the definition of hypofibrinolysis. Differences between the hypercoagulable (HC) and non-hypercoagulable groups remained apparent at 48 hours after anticoagulation. At this time point, the K time was significantly lower (p ˂ 0,01), and the α-angle (p ˂ 0,01) and maximum amplitude (MA) (p ˂ 0,01) were significantly higher in the HC cohort. At resolution of hypoxia, or day 10, only MA was significantly higher in the hypercoagulable group compared to the non-hypercoagulable group (p = 0.01). The initial impairment in fibrinolysis (Ly30), α angle, and MA were significantly associated with mortality, with p values of 0.006, 0.031, and 0.04, respectively. CONCLUSIONS: In this South African population, hypercoagulability was a highly prevalent phenomenon in COVID-19 disease. It was typified by hypofibrinolysis and a persistently elevated MA, despite anticoagulation therapy.

Artesunate for the treatment of severe malaria: A retrospective review of patients admitted to two tertiary hospital intensive care units in Johannesburg, South Africa.

BACKGROUND: Globally, malaria is one of the six major causes of deaths from communicable diseases. In South Africa, malaria is known to be endemic in three provinces. Two large trials, AQUAMAT and SEAQUAMAT, demonstrated the superiority of intravenous (IV) artesunate compared to quinine. A systematic review (including the above trials) demonstrated a mortality benefit for adult patients treated with artesunate, but included studies that were conducted in Asia with no adult data available for Africa. Given the lack of local data, we conducted this study to investigate the use of artesunate for the treatment of severe malaria at two academic adult intensive care units (ICUs) in Johannesburg. METHODS: We undertook a retrospective patient record review. All patients admitted to the two ICUs and treated for severe malaria using artesunate were included. The study period extended from April 2010 to April 2014. The primary outcome was to determine the observed mortality and relate it to the predicted mortality based on the Acute Physiology and Chronic Health Evaluation (APACHE II) severity of illness score. The ratio of the observed mortality to the expected mortality based on the APACHE II severity of illness score provides a standardised mortality ratio (SMR). Clinical and laboratory parameters data were analysed. RESULTS: There were 56 patients included in the study, of which 40 were male (71.4%). The mean APACHE II score was 19 (standard deviation 5.4). We observed a lower than predicted mortality rate of 21.4% (SMR 0.66). Human immunodeficiency virus (HIV) was the most prevalent comorbidity (32%). There was no travel history in 26.8% of patients. Heart rate, respiratory rate and Glasgow Coma Scale (GCS) all improved significantly from admission to the time of discharge (p ≤ 0.01). Acidaemia, bilirubin, urea and bleeding risk (platelet count) also improved (p ≤ 0.01). Mechanical ventilation was associated with an increased risk of death (OR 35; CI 7.0-182). CONCLUSION: In this retrospective two-centre study, IV artesunate was associated with a lower than predicted mortality in adult patients with severe malaria requiring ICU admission.

Vitamin D status and COVID-19 severity

Background: Age, body mass index (BMI) and pre-existing comorbidities are known risk factors of severe coronavirus disease 2019 (COVID-19). In this study we explore the relationship between vitamin D status and COVID-19 severity. Methods: We conducted a prospective, cross-sectional descriptive study. We enrolled 100 COVID-19 positive patients admitted to a tertiary level hospital in Johannesburg, South Africa. Fifty had symptomatic disease (COVID-19 pneumonia) and 50 who were asymptomatic (incidental diagnosis). Following written informed consent, patients were interviewed regarding age, gender and sunlight exposure during the past week, disease severity, BMI, calcium, albumin, magnesium and alkaline phosphatase levels. Finally, blood was collected for vitamin D measurement. Results: We found an 82% prevalence rate of vitamin D deficiency or insufficiency among COVID-19 patients. Vitamin D levels were lower in the symptomatic group (18.1 ng/mL ± 8.1 ng/mL) than the asymptomatic group (25.9 ng/mL ± 7.1 ng/mL) with a p-value of 0.000. The relative risk of symptomatic COVID-19 was 2.5-fold higher among vitamin D deficient patients than vitamin D non-deficient patients (confidence interval [CI]: 1.14­3.26). Additional predictors of symptomatic disease were older age, hypocalcaemia and hypoalbuminaemia. Using multiple regression, the only independent predictors of COVID-19 severity were age and vitamin D levels. The patients exposed to less sunlight had a 2.39-fold increased risk for symptomatic disease compared to those with more sunlight exposure (CI: 1.32­4.33). Conclusion: We found a high prevalence of vitamin D deficiency and insufficiency among patients admitted to hospital with COVID-19 and an increased risk for symptomatic disease in vitamin D deficient patients.