Early net ultrafiltration rate and mortality in critically ill patients receiving continuous renal replacement therapy.

BACKGROUND: In patients treated with continuous renal replacement therapy (CRRT), early net ultrafiltration (NUF) rates may be associated with differential outcomes. We tested whether higher early NUF rates are associated with increased mortality in CRRT patients. METHODS: We performed a retrospective, observational study of all patients treated with CRRT within 14 days of intensive care unit admission. We defined the early (first 48 h) NUF rate as the volume of fluid removed per hour adjusted for patient body weight and analysed as a categorical variable (>1.75, 1.01-1.75 and <1.01 mL/kg/h). The primary outcome was 28-day mortality. To deal with competing risk, we also compared different time epochs. RESULTS: We studied 347 patients {median age 64 [interquartile range (IQR) 53-71] years and Acute Physiology and Chronic Health Evaluation III score 73 [IQR 54-90]}. Compared with NUF rates <1.01 mL/kg/h, NUF rates >1.75 mL/kg/h were associated with greater mortality rates in each epoch: Days 0-5, adjusted hazard ratio (aHR) 1.27 [95% confidence interval (CI) 1.21-1.33]; Days 6-10, aHR 1.62 (95% CI 1.55-1.68); Days 11-15, aHR 1.87 (95% CI 1.79-1.94); Days 16-26, aHR 1.92 (95% CI 1.84-2.01) and Days 27-28, aHR 4.18 (95% CI 3.98-4.40). For every 0.5 mL/kg/h NUF rate increase, mortality similarly increased during these epochs. CONCLUSION: Compared with early NUF rates <1.01 mL/kg/h, NUF rates >1.75 mL/kg/h are associated with increased mortality. These observations provide the rationale for clinical trials to confirm or refute these findings.

Relative Hypoglycemia in Diabetic Patients With Critical Illness.

OBJECTIVES: Relative hypoglycemia is a decrease in glucose greater than or equal to 30% below prehospital admission levels (estimated by hemoglobin A1C) but not to absolute hypoglycemia levels. It is a recognized pathophysiologic phenomenon in ambulant poorly controlled diabetic patients but remains unexamined during critical illness. We examined the frequency, characteristics, and outcome associations of relative hypoglycemia in diabetic patients with critical illness. DESIGN: Retrospective cohort study. SETTING: ICU of a tertiary hospital. PATIENTS: One-thousand five-hundred ninety-two critically ill diabetic patients between January 2013 and December 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The median age of patients was 67 years (interquartile range, 60-75 yr). The median Acute Physiology and Chronic Health Evaluation III score was 53 (interquartile range, 40-68). Thirty-four percent of patients with diabetes experienced relative hypoglycemia (exposure) during their ICU admission. Such patients had higher glycemic lability, hemoglobin A1C levels, and Acute Physiology and Chronic Health Evaluation III scores. The hazard ratio for 28-day mortality of diabetic patients, censored at hospital discharge, for patients with relative hypoglycemia was 1.9 (95% CI, 1.3-2.8) and was essentially unchanged after adjustment for episodes of absolute hypoglycemia. After an episode of relative hypoglycemia, the hazard ratio for subsequent absolute hypoglycemia in the ICU was 3.5 (95% CI, 2.3-5.3). CONCLUSIONS: In ICU patients with diabetes, relative hypoglycemia is common, increases with higher hemoglobin A1C levels, and is a modifiable risk factor for both mortality and subsequent absolute hypoglycemia. These findings provide the rationale for future interventional studies to explore new blood glucose management strategies and to substantiate the clinical relevance of relative hypoglycemia.

Mediators of the Impact of Hourly Net Ultrafiltration Rate on Mortality in Critically Ill Patients Receiving Continuous Renal Replacement Therapy.

OBJECTIVES: During continuous renal replacement therapy, a high net ultrafiltration rate has been associated with increased mortality. However, it is unknown what might mediate its putative effect on mortality. In this study, we investigated whether the relationship between early (first 48 hr) net ultrafiltration and mortality is mediated by fluid balance, hemodynamic instability, or low potassium or phosphate blood levels using mediation analysis and the primary outcome was hospital mortality. DESIGN: Retrospective, observational study. SETTING: Mixed medical and surgical ICUs at Austin hospital, Melbourne, Australia. PATIENTS: Critically ill patients treated with continuous renal replacement therapy within 14 days of ICU admission who survived greater than 48 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We studied 347 patients (median [interquartile range] age: 64 yr [53-71 yr] and Acute Physiology and Chronic Health Evaluation III score: 73 (54-90)]. After adjustment for confounders, compared with a net ultrafiltration less than 1.01 mL/kg/hr, a net ultrafiltration rate greater than 1.75 mL/kg/hr was associated with significantly greater mortality (adjusted odds ratio, 1.15; 95% CI, 1.03-1.29; p = 0.011). Adjusted univariable mediation analysis found no suggestion of a causal mediation pathway for this effect by blood pressure, vasopressor therapy, or potassium levels, but identified a possible mediation effect for fluid balance (average causal mediation effect, 0.95; 95% CI, 0.89-1.00; p = 0.060) and percentage of phosphate measurements with hypophosphatemia (average causal mediation effect, 0.96; 95% CI, 0.92-1.00; p = 0.055). However, on multiple mediator analyses, these two variables showed no significant effect. In contrast, a high net ultrafiltration rate had an average direct effect of 1.24 (95% CI, 1.11-1.40; p < 0.001). CONCLUSIONS: An early net ultrafiltration greater than 1.75 mL/kg/hr was independently associated with increased hospital mortality. Its putative effect on mortality was direct and not mediated by a causal pathway that included fluid balance, low blood pressure, vasopressor use, hypokalemia, or hypophosphatemia.

Hourly Fluid Balance in Patients Receiving Continuous Renal Replacement Therapy.

INTRODUCTION: Little is known about early (first 48 h) hourly and cumulative fluid balance (FB) during continuous renal replacement therapy (CRRT). OBJECTIVES: To study the characteristics and outcome associations of early hourly and cumulative FB. METHODS: We studied FB in CRRT patients (2016-2018). RESULTS: Among 350 patients, mean hourly FB became negative after 20 CRRT hours, but within 6 CRRT hours in patients with baseline fluid overload. A negative early FB was never achieved in patients receiving vasopressor therapy (p < 0.001). Mortality was 31%. The percentage of hourly negative FB was independently associated with decreased ICU mortality. A time-weighted hourly FB between 18.5 and -33 mL/h was also significantly and independently associated with decreased mortality. CONCLUSIONS: In CRRT patients, an early FB conservative approach is possible, modulated by patient characteristics, and associated with a low mortality. Moreover, avoidance of an early positive FB is associated with decreased mortality.

Radiologically and clinically diagnosed acute pulmonary oedema in critically ill patients: prevalence, patient characteristics, treatments and outcomes.

Background: Acute pulmonary oedema is a life-threatening syndrome diagnosed based on radiological and clinical findings. However, to our knowledge, no studies have investigated this syndrome in critically ill patients. Objective: To describe the prevalence of radiologically and clinically diagnosed pulmonary oedema (RCDPO) in critically ill patients, characteristics of diagnosed patients, and treatments and outcomes in this patient population. Methods: We conducted a retrospective study using natural language processing to identify all radiological reports of pulmonary oedema among patients who had been admitted to single tertiary intensive care unit (ICU) over a 1-year period (January 2015 to January 2016). We reviewed clinical data, discharge diagnosis, treatment and outcomes for such patients, and used multivariable logistic regression analysis to identify the association of RCDPO with various outcomes. Results: Out of 2001 ICU patients, we identified 238 patients (11.9%) with RCDPO. Patients with RCDPO were more acutely ill, had more chronic liver disease and had more chronic renal failure than critically ill patients who did not have RCDPO. They were typically admitted with acute cardiovascular disease; were more likely to receive invasive mechanical ventilation and continuous renal replacement therapy; had longer duration of ICU and hospital stay; were more likely to die in hospital; and, if discharged alive, were more likely to be admitted to a chronic care facility. In total, 46 RCDPO patients (19.3%) died in hospital. On multivariable analysis, only age and continuous renal replacement therapy were independently associated with mortality. In contrast, invasive mechanical ventilation was associated with a 2.5 times greater odds of radiological resolution. Conclusion: RCDPO affected about one in eight ICU patients. Such patients were sicker and had more comorbidities. The presence of RCDPO was independently associated with higher risk of death. Invasive mechanical ventilation was the only intervention independently associated with greater odds of radiological resolution.

Chewing gum prophylaxis for postoperative nausea and vomiting in the intensive care unit: a pilot randomised controlled trial.

Objective: To test the effectiveness of chewing gum in the prophylaxis of postoperative nausea and vomiting (PONV) in patients admitted to the intensive care unit (ICU) after surgery. Design: Prospective, open label, pilot randomised controlled trial. Setting: Two metropolitan ICUs. Participants: Ninety postoperative adult patients admitted to the ICU. Intervention: Patients administered chewing gum, who chewed for at least 15 minutes every 4 hours, were compared with a control group, who were administered a 20 mL sip of water orally every 4 hours. Main outcome measures: The primary outcome was the number of patient-reported episodes of nausea in the first 24 hours after the operation. Secondary outcomes included vomiting or dry retching episodes, and duration and severity of nausea. Results: Forty-six patients were randomly allocated to chewing gum and 44 patients to water. There was no difference between groups in the number of patients with nausea (10 [22%] chewing gum v 12 [27%] control patients; P = 0.72), nausea episodes (22 episodes; [median, 0; IQR, 0-0] v 21 episodes [median, 0; IQR, 0-1] per patient in each group respectively), vomiting/retching (2 [4%] chewing gum v 6 [14%] control patients; P = 0.24), or duration/severity of nausea. Conclusion: Regular postoperative administration of chewing gum in a surgical ICU patient cohort did not reduce nausea, vomiting or retching. The prevalence of PONV is less than previously reported. Our findings can inform future studies of PONV prophylaxis in post-surgical ICU patients. Trial registration: Australian New Zealand Clinical Trial Registry No. ACTRN12617001185358.