Early Lactate Clearance as a Determinant of Survival in Patients with Sepsis: Findings from a Low-resource Country.

Background: Single lactate measurements have been reported to have prognostic significance, however, there is a lack of data in local literature from Pakistan. This study was done to determine prognostic role of lactate clearance in sepsis patients being managed in our lower-middle income country. Methods: This prospective cohort study was conducted from September 2019-February 2020 at the Aga Khan University Hospital, Karachi. Patients were enrolled using consecutive sampling and categorized based on their lactate clearance status. Lactate clearance was defined as decrease by 10% or greater in repeat lactate from the initial measurement (or both initial and repeat levels <=2.0 mmol/L). Results: A total 198 patients were included in the study, 51% (101) were male. Multi-organ dysfunction was reported in 18.6% (37), 47.7% (94) had single organ dysfunction, and 33.8% (67) had no organ dysfunction. Around 83% (165) were discharged and 17% (33) died. There were missing data for 25.8% (51) of the patients for the lactate clearance, whereas 55% (108) patients had early lactate clearance and 19.7% (39) had delayed lactate clearance.On univariate analysis, mortality rate was higher in patients with delayed lactate clearance (38.4% vs 16.6%) and patients were 3.12 times (OR = 3.12; [95% CI: 1.37-7.09]) more likely to die as compared with early lactate clearance. Patients with delayed lactate clearance had higher organ dysfunction (79.4% vs 60.1%) and were 2.56 (OR = 2.56; [95% CI: 1.07-6.13]) times likely to have organ dysfunction. On multivariate analysis, after adjusting for age and co-morbids, patients with delayed lactate clearance were 8 times more likely to die than patients with early lactate clearance [aOR = 7.67; 95% CI:1.11-53.26], however, there was no statistically significant association between delayed lactate clearance [aOR = 2.18; 95% CI: 0.87-5.49)] and organ dysfunction. Conclusion: Lactate clearance is a better determinant of sepsis and septic shock effective management. Early lactate clearance is related to better outcomes in septic patients.

Clinical Features and Outcomes of Acute Chlorine Gas Inhalation; a Brief Report.

Introduction: On March 6th,2020, chlorine gas leak was reported at Engro Polymer & Chemicals Plant in Karachi City, Pakistan. This study aimed to evaluate the clinical features and outcomes of patients who presented to emergency department (ED) following this event. Methods: This retrospective cross-sectional study, evaluated the clinical features and outcomes (length of hospital stay, complications, and mechanical ventilation requirement) of patients presenting to ED of Aga Khan University Hospital, Karachi, Pakistan, with history of chlorine gas exposure at the Engro Plant from 6th March to 14th March 2020. Results: 38 patients with mean age of 33.1 ± 8.1 years presented to ED with history of chlorine gas exposure (100% male). 4 (10.5%) cases had comorbid diseases. Most common presenting symptom was dyspnea, observed in 33 (86.8%) cases, followed by cough, seen in 27 (71.1%) subjects. 13.2% (5/38) patients had infiltration on chest x-ray and 33 (86.8 %) required hospitalization. 6 (15.8%) patients had repeat presentation requiring hospitalization or ED visit. 18 (47.4%) were managed with high flow oxygen therapy, 9 (23.7%) required non-invasive ventilation and one patient was intubated due to development of pneumo-mediastinum. Mean length of stay was 1.55 ± 1.58 days and no patients died. Presence of tachycardia was the only finding significantly associated with need for oxygen (p = 0.033) and non-invasive ventilation (p = 0.012). Conclusion: The majority of patients presenting with acute chlorine gas exposure showed good clinical outcomes and rapid recovery, however, a high index of suspicion and vigilance should be maintained for complications such as pneumomediastinum and acute respiratory distress syndrome in these patients.

Clinical Characteristics and Outcomes of COVID-19 Acute Respiratory Distress Syndrome Patients Requiring Invasive Mechanical Ventilation in a Lower Middle-Income Country.

Background: COVID-19 related acute respiratory distress syndrome (ARDS) requires intensive care, which is highly expensive in lower-income countries. Outcomes of COVID-19 patients requiring invasive mechanical ventilation in Pakistan have not been widely reported. Identifying factors forecasting outcomes will help decide optimal care levels and prioritise resources. Methods: A single-centre, retrospective study on COVID-19 patients requiring invasive mechanical ventilation was conducted from 1st March to 31st May 2020. Demographic variables, physical signs, laboratory values, ventilator parameters, complications, length of stay, and mortality were recorded. Data were analysed in SPSS ver.23. Results: Among 71 study patients, 87.3% (62) were males, and 12.7% (9) were females with a mean (SD) age of 55.5(13.4) years. Diabetes mellitus and hypertension were the most common comorbidities in 54.9% (39) patients. Median(IQR) SOFA score on ICU admission and at 48 hours was 7(5-9) and 6(4-10), and median (IQR) APACHE-II score was 15 (11-24) and 13(9-23), respectively. Overall, in-hospital mortality was 57.7%; 25% (1/4), 55.6% (20/36) and 64.5% (20/31) in mild, moderate, and severe ARDS, respectively. On univariate analysis; PEEP at admission, APACHE II and SOFA score at admission and 48 hours; Acute kidney injury; D-Dimer>1.5 mg/L and higher LDH levels at 48 hours were significantly associated with mortality. Only APACHE II scores at admission and D-Dimer levels> 1.5 mg/L were independent predictors of mortality on multivariable regression (p-value 0.012 & 0.037 respectively). Admission APACHE II scores, Area under the ROC curve for mortality was 0.80 (95%CI 0.69-0.90); sensitivity was 77.5% and specificity 70% (cut-off ≥13.5). Conclusion: There was a high mortality rate in severe ARDS. The APACHE II score can be utilised in mortality prediction in COVID-19 ARDS patients. However, larger-scale studies in Pakistan are required to assess predictors of mortality.

Spontaneous pneumomediastinum in accidental chlorine gas inhalational injury: case report and review of literature.

A young man presented in emergency department with shortness of breath and cough after accidental inhalation of chlorine gas. Initial presentation was unremarkable; therefore, he was kept under observation for 8 hours and was later discharged. After 5 hours, the patient presented again in emergency department with sudden-onset shortness of breath and chest discomfort. On examination, subcutaneous crepitation around the neck and chest was found. Chest and neck X-ray revealed subcutaneous emphysema and pneumomediastinum. CT neck and chest was done, which revealed subcutaneous emphysema and pneumomediastinum and a linear air density in close approximation to right posterolateral wall of trachea at the level of superior margin of sternum was reported. These findings raised the possibility of tracheal injury which was later confirmed by fiberoptic laryngoscopy. The patient was intubated due to hypercapnic respiratory failure resulting from hypoventilation and respiratory distress. Bilateral chest tube insertion was done due to worsening subcutaneous emphysema, high ventilator parameters and prevention of progression to pneumothorax. He was extubated after 5 days; bilateral chest tubes were removed before discharge and underwent uneventful recovery.

Black stone poisoning with a unique complication of posterior reversible encephalopathy syndrome (PRES).

A 25-year-old woman presented to the emergency department with difficulty in breathing, within 12 hours of intentional black stone ingestion, that is, para-phenylenediamine (p-PD), a chemical component of hair dye. Video laryngoscopy was done which showed laryngeal oedema and got intubated immediately to prevent respiratory failure. She got admitted to the intensive care unit and rigorous fluid resuscitation was done due to acute kidney injury secondary to rhabdomyolysis. On the 5th day, she got extubated after a successful spontaneous breathing trial, and step down to the high dependency unit, where she had four episodes of seizures in a day. After antiepileptic medication initiation, seizures were settled, brain imaging done to rule out stroke showed a finding suggestive of posterior reversible encephalopathy syndrome. Adequate intravenous fluid resuscitation was performed and blood pressure monitored closely. She remained vitally stable and clinically better hence discharge home with clinic follow-up on the 9th day of hospitalisation.

Neutrophils to Lymphocyte Ratio: Earliest and Efficacious Markers of Sepsis.

Background Neutrophil to lymphocyte ratio (NLR) can be easily calculated from the white cell differential count and is considered an auspicious marker for predicting different diseases, including sepsis. In this study, we aimed to compare the efficacy of NLR as a sepsis marker by comparing it with other markers of sepsis, such as C-reactive protein (CRP), procalcitonin, and the Sequential Organ Failure Assessment (SOFA) score. Methods A cross-sectional analytical study was conducted at the Aga Khan University Hospital from July 2019 to December 2019. A total of 168 patients who were admitted to the medicine department with a diagnosis of sepsis on arrival or during the hospital stay were enrolled. The neutrophil to lymphocyte ratio was calculated to form venous samples taken on admission and compared to the level of CRP, procalcitonin, culture reports, and the SOFA score as a predictor of sepsis. Results Out of 168 patients, 55.3% were male. The median age of the participants was 68.40 (interquartile range (IQR): 19.5) years in males and 64.0 (IQR: 18.0) in females. Procalcitonin was performed in 121 (72%) and CRP performed in 61 (36.3%) patients. The NLR showed significant associations with all the tested lab parameters of sepsis, such as CRP (p = 0.02), procalcitonin (p = 0.01), and SOFA score (p = 0.01). Values when analyzed according to culture-positive showed higher values in culture-positive samples but were not statistically significant. Conclusion Neutrophil to lymphocyte ratio is a cheap and rapidly available predictor of sepsis and has shown a significant correlation with other relatively expensive and non-rapidly existing markers of inflammation and sepsis. However, large prospective studies are needed to prove its real effectiveness as a marker of sepsis and its prognosis.

Outcome of COVID-19 patients with use of Tocilizumab: A single center experience.

COVID-19 pandemic has become a global concern. Cytokine release syndrome (CRS) complicates acute respiratory distress syndrome (ARDS) and causes multi-organ failure which can subsequently lead to mortality in COVID-19 patients. Tocilizumab, an interleukin-6 antagonist, has shown to salvage patients with cytokine release storm. In this study, we aim to evaluate therapeutic response of Tocilizumab in COVID-19 patients. A single-arm retrospective review of 40 patients with COVID-19, admitted to The Aga Khan University Hospital Karachi, from March 2020 to May 2020 was performed. Selection of patients for use of Tocilizumab was based on severity of disease, rapid clinical deterioration, presence of CRS and absence of any absolute contraindication to Tocilizumab. Improvement after Tocilizumab was defined as improvement in oxygen requirement and inflammatory parameters. Serum levels of inflammatory cytokines like C-reactive protein, ferritin, D-dimer and lactate dehydrogenase levels were monitored before and after administering Tocilizumab. Mean age was 62.4 years and 33 (82.5%) were male. 19 (47.5%) patients were critically sick, 18 (45%) were severely sick and 3 (7.5%) were moderately sick. 29 (77.5%) patients showed significant improvement in oxygen requirement, inflammatory parameters and chest x-rays, out of which 28 patients were discharged home. The mean duration between administration of Tocilizumab and overall improvement was 4.3 ± 3.2 days. Hence, Tocilizumab can be used as a possible treatment option in patients with COVID-19 induced CRS but needs monitoring for its adverse effects.

A Fatal Case of Primary Amoebic Meningoencephalitis (PAM) Complicated with Diabetes Insipidus (DI): A Case Report and Review of the Literature.

Naegleria fowleri is a highly infective free-living amoeba usually isolated from soil and fresh water and is primarily found to infect the central nervous system (CNS) resulting in primary amoebic meningoencephalitis (PAM). PAM as a cause of meningitis is often overlooked for other, more common causes of meningitis. Despite all the advances in antimicrobial therapy and supportive care systems, the mortality rate of this rare infection remains above 95% with the bulk of the cases being found in developed countries. We are presenting a case of a 44-year-old male with fever, worsening headache, and generalized weakness. Lumbar puncture showed a raised leucocyte count of 1100/µL with predominant polymorphonuclear cells, and wet mount prep for Naegleria fowleri was positive further confirmed with PCR. The patient was started Intravenous (IV) and intrathecal amphotericin-B, Per Oral (PO) miltefosine, IV rifampin, IV fluconazole, and IV dexamethasone. However, the patient started producing urine at 300-500 ml/hour. The patient's sodium levels increased from 144 to 175 mmol/L in 12 hours with raised serum osmolality and decreased urine osmolality and urine sodium. The patient was started on PO desmopressin of 0.2 micrograms twice daily after which his urine output dropped to 60-80 ml/hour and sodium decreased from 175 to 162 and, later 155 mmol/L; however, the patient expired. PAM is a rare and extremely fatal illness, but with increasing incidence now being reported in developing countries as a result of better diagnostics. DI is a very rare complication reported in these patients leading to poor outcome. The complication of diabetes insipidus (DI) has not been extensively studied in patients having PAM. Only three cases have been reported with this complication. No mechanism has been mentioned in the literature behind the development of DI in these patients, and no study has mentioned laboratory details of DI as mentioned in this report.

Bomb Blast and Its Consequences: Successful Intensive Care Management of Massive Pulmonary Embolsim.

A suicide bomb blast in 2013 at a distant city of Pakistan killed 84 and wounded more than 150 people. Some patients were transferred to our tertiary care hospital because of extreme load on medical services there. This patient arrived at the Aga Khan Hospital, 2 days after the bomb blast injury and underwent an orthopedic procedure. Next day, he developed sudden tachypnea, desaturation, and circulatory collapse. After initial cardiopulmonary resuscitation, he was immediately transferred to surgical intensive care unit. Based on history, echocardiography findings and patient parameters, a clinical diagnosis of massive pulmonary embolism was made and immediate thrombolytic therapy with alteplase was started. The immediate improvement in hemodynamic status was evident following 2 hours of alteplase infusion. This case also highlights the aggressiveness of resuscitation, decision making in initiating thrombolytic therapy on clinical grounds, importance of deep venous thrombosis prophylaxis, and exhaustion of health resources due to blast related mass destruction.

Occurrence of hypoxia in the wards of a teaching hospital.

OBJECTIVE: Appearance of hypoxia in a patient may be an indicator of a serious medical condition that can have grave consequences. Clinical evaluation fails to detect majority of the patients of hypoxia, and therefore, it may remain unnoticed in the wards. We planned to assess the magnitude of hypoxia in different wards of our tertiary care hospital. MATERIALS AND METHODS: We studied all the patients admitted in various medical and surgical wards during 1 week of study. Oxygen saturation (SpO(2)) was measured with the help of a pulse oximeter in all the patients who remained admitted for at least 24 h. Hypoxia was diagnosed in a patient when he had SpO(2) less than 90%. RESULTS: During the study period, 1167 patients were admitted in various wards of the hospital. Hypoxia was detected in 121 patients (10.36%). Among them, 7 (0.59%) patients were already having a diagnosis of respiratory failure, but were not on oxygen therapy while 5 (0.42%) patients were having SpO(2) less than 90% despite of oxygen therapy. In 109 (9.34%) patients, hypoxia was detected incidentally. CONCLUSION: Unnoticed hypoxia was detected in a significant number of the patients admitted in the wards of the hospital. Therefore, it is concluded that oxygen saturation measurements should be included with other vital parameters like pulse, temperature, and blood pressure, in the monitoring chart of all the admitted patients.

Enteric pathogens in HIV-positive patients with diarrhoea and their correlation with CD4+ T-lymphocyte counts.

BACKGROUND AND OBJECTIVES: Opportunistic parasitic infections are among the most serious infections in human immunodeficiency virus (HIV) positive patients and claim number of lives every year. The present study was conducted to determine the prevalence of intestinal parasites and to elucidate the association between intestinal opportunistic parasitic infection and CD4 (CD4+ T lymphocyte) counts in HIV-positive patients. MATERIALS AND METHODS: The study was done on 266 HIV-positive patients presenting with diarrhoea and 100 HIV-positive patients without diarrhoea attending the integrated counselling and testing centre (ICTC) of SMS hospital, Jaipur. Simultaneously, CD4+ T-cell count estimation was done to assess the status of HIV infection vis-à-vis parasitic infections. The identification of pathogens was done on the basis of direct microscopy and different staining techniques. RESULTS: Out of 266 patients with diarrhoea, parasites were isolated from 162 (i.e. 60.9%) patients compared to 16 (16%) patients without diarrhoea. Cryptosporidium parvum (25.2%) was the predominant parasite isolated in HIV-positive patients with diarrhoea followed by Isospora belli (10.9%). Parasites were more commonly isolated from stool samples of chronic diarrhoea patients, (77% i.e. 128/166) as compared to acute diarrhoea patients (34% i.e. 34/100) (P<0.05). The maximum parasitic isolation was in the patients with CD4+ T cell counts below 200 cells/µl. CONCLUSIONS: Chronic diarrhoea in HIV-positive patients with CD4+ T-cell counts <200/µl has high probability of association with intestinal parasitic infections. Identification of these parasitic infections may play an important role in administration of appropriate therapy and reduction of mortality and morbidity in these patients.