Recommendations for sepsis management in resource-limited settings

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

An investigation into the effects of commencing haemodialysis in the critically ill

<b>Introduction:</b> We have aimed to describe haemodynamic changes when haemodialysis is instituted in the critically ill. 3 hypotheses are tested: 1)The initial session is associated with cardiovascular instability, 2)The initial session is associated with more cardiovascular instability compared to subsequent sessions, and 3)Looking at unstable sessions alone, there will be a greater proportion of potentially harmful changes in the initial sessions compared to subsequent ones. <b>Methods:</b> Data was collected for 209 patients, identifying 1605 dialysis sessions. Analysis was performed on hourly records, classifying sessions as stable/unstable by a cutoff of >+/-20% change in baseline physiology (HR/MAP). Data from 3 hours prior, and 4 hours after dialysis was included, and average and minimum values derived. 3 time comparisons were made (pre-HD:during, during HD:post, pre-HD:post). Initial sessions were analysed separately from subsequent sessions to derive 2 groups. If a session was identified as being unstable, then the nature of instability was examined by recording whether changes crossed defined physiological ranges. The changes seen in unstable sessions could be described as to their effects: being harmful/potentially harmful, or beneficial/potentially beneficial. <b>Results:</b> Discarding incomplete data, 181 initial and 1382 subsequent sessions were analysed. A session was deemed to be stable if there was no significant change (>+/-20%) in the time-averaged or minimum MAP/HR across time comparisons. By this definition 85/181 initial sessions were unstable (47%, 95% CI SEM 39.8-54.2). Therefore Hypothesis 1 is accepted. This compares to 44% of subsequent sessions (95% CI 41.1-46.3). Comparing these proportions and their respective CI gives a 95% CI for the standard error of the difference of -4% to 10%. Therefore Hypothesis 2 is rejected. In initial sessions there were 92/1020 harmful changes. This gives a proportion of 9.0% (95% CI SEM 7.4-10.9). In the subsequent sessions there were 712/7248 harmful changes. This gives a proportion of 9.8% (95% CI SEM 9.1-10.5). Comparing the two unpaired proportions gives a difference of -0.08% with a 95% CI of the SE of the difference of -2.5 to +1.2. Hypothesis 3 is rejected. Fisher’s exact test gives a result of p=0.68, reinforcing the lack of significant variance. <b>Conclusions:</b> Our results reject the claims that using haemodialysis is an inherently unstable choice of therapy. Although proportionally more of the initial sessions are classed as unstable, the majority of MAP and HR changes are beneficial in nature

Effect of pediatric ventilation weaning technique on work of breathing

BACKGROUND: Ventilator liberation is one of the most challenging aspects in patients with respiratory failure. Most patients are weaned through a transition from full to partial respiratory support, whereas some advocate using a continuous spontaneous ventilation (CSV). However, there is little scientific evidence supporting the practice of pediatric ventilator liberation, including the timing of onset of and the approach to weaning mode. We sought to explore differences in patient effort between a pressure controlled continuous mode of ventilation (PC-CMV) [in this cohort PC assist/control (PC-A/C)] with a reduced ventilator rate and CSV, and to study changes in patient effort with decreasing PS. METHODS: In this prospective physiology cross-over study, we randomized children < 5 years to first PC-A/C with a 25% reduction in ventilator rate, or CSV (continuous positive airway pressure [CPAP] + PS). Patients were then crossed over to the other arm. Patient effort was measured by calculating inspiratory work of breathing (WOB) using the Campbell diagram (WOBCampbell), and by pressure-rate-product (PRP) and pressure-time-product (PTP). Respiratory inductance plethysmography (RIP) was used to calculate the phase angle. Measurements were obtained at baseline, during PC-A/C and CPAP + PS, and during decreasing set PS (maximum -6 cmH2O). RESULTS: Thirty-six subjects with a median age of 4.4 (IQR 1.5-11.9) months and median ventilation time of 4.9 (IQR 3.4-7.0) days were included. Nearly all patients (94.4%) were admitted with primary respiratory failure. WOBCampbell during baseline [0.67 (IQR 0.38-1.07) Joules/L] did not differ between CSV [0.49 (IQR 0.17-0.83) Joules/L] or PC-A/C [0.47 (IQR 0.17-1.15) Joules/L]. Neither PRP, PTP, ∆Pes nor phase angle was different between the two ventilator modes. Reducing pressure support resulted in a statistically significant increase in patient effort, albeit that these differences were clinically negligible. CONCLUSIONS: Patient effort during pediatric ventilation liberation was not increased when patients were in a CSV mode of ventilation compared to a ventilator mode with a ventilator back-up rate. Reducing the level of PS did not lead to clinically relevant increases in patient effort. These data may aid in a better approach to pediatric ventilation liberation. Trial registration clinicaltrials.gov NCT05254691. Registered 24 February 2022

PROTOCOLIZED VOLUME DE-RESUSCITATION IN CRITICALLY ILL PATIENTS

While early fluid resuscitation may be a necessary component to decrease mortality in the majority of critically ill patients admitted to the intensive care unit, the benefit of continued administration after the first 24 hours is less clear. Paradoxically, a positive fluid balance secondary to intravenous fluid receipt has been associated with diverse and persistent perpetuating detriment on a multitude of organ systems. Continued clinical harm has been demonstrated on pulmonary and renal function as well as patient outcomes such as rates of mortality and length of stay. Despite the growing body of evidence supporting the potential adverse aspects of positive fluid balances, fluid overload remains common in patients during the early days of critical care admission. One approach to correcting fluid balance is shifting focus onto the post- or de- resuscitation period with appropriate fluid removal with diuresis once hemodynamic stability is achieved. However, diuresis is often ineffective due to a lack of standardization in identification of fluid-overloaded patients. Further, optimal transition times between fluid resuscitation and fluid removal are not clear and physical signs of fluid overload are delayed relative to onset of organ damage. While administration of diuretics has shown to decrease net volume and improve clinical outcomes in the critically ill, current practice does not reflect clinical trial findings. Most treatment regimens are often inadequate both by nature of time and dosing intensity. Further, as de-resuscitation occurs once the initial instability has resolved, precedence is usually given to other acute or critical needs rather than follow-up for diuresis effectiveness. Additionally, frequent apprehension for medication side effects is seen, despite the preponderance of adverse event data found only in non-critical care populations, frequently non-translatable to patients within the intensive care unit. Optimization of diuresis in critically ill patients is primed for clinical pharmacy intervention. Clinical pharmacists are experts in the delivery of pharmaceutical care, utilizing specialized therapeutic knowledge, experience, and judgment to ensure optimal patient outcomes. Pharmacist-driven protocols for other conditions have shown improved patient outcomes, reduced adverse events and improved target attainment in before and after studies. A pharmacist- driven diuresis protocol to facilitate de-resuscitation implemented within the multidisciplinary critical care team has the potential to improve patient care by optimizing pharmacotherapy selection, while potentially reducing adverse events, days on mechanical ventilation and length of intensive care unit stay. Such a protocol rightfully places pharmacist accountability on medication-related outcomes while potentially decreasing critical care resource utilization. The work within this dissertation aims to accomplish the development of a pharmacist- driven diuresis protocol for implementation in the medical intensive care unit, with national pharmacy organization sponsorship. Further, the protocol aims to be adopted as an innovative practice change for de-resuscitation of critically ill patients to improve clinical outcomes while advancing the pharmacy profession