Effect of Transfusion of Red Blood Cells With Longer vs Shorter Storage Duration on Elevated Blood Lactate Levels in Children With Severe Anemia: The TOTAL Randomized Clinical Trial. (Sirignano)

Dhabangi A, et al. Effect of Transfusion of Red Blood Cells With Longer vs Shorter Storage Duration on Elevated Blood Lactate Levels in Children With Severe Anemia: The TOTAL Randomized Clinical Trial. JAMA. 2015 Dec 15;314(23):2514-23.

IMPORTANCE: Although millions of transfusions are given annually worldwide, the effect of red blood cell (RBC) unit storage duration on oxygen delivery is uncertain.

OBJECTIVE: To determine if longer-storage RBC units are not inferior to shorter-storage RBC units for tissue oxygenation as measured by reduction in blood lactate levels and improvement in cerebral tissue oxygen saturation among children with severe anemia.

DESIGN, SETTING, AND PARTICIPANTS: Randomized noninferiority trial of 290 children (aged 6-60 months), most with malaria or sickle cell disease, presenting February 2013 through May 2015 to a university-affiliated national referral hospital in Kampala, Uganda, with a hemoglobin level of 5 g/dL or lower and a lactate level of 5 mmol/L or higher.

INTERVENTIONS: Patients were randomly assigned to receive RBC units stored 25 to 35 days (longer-storage group; n = 145) vs 1 to 10 days (shorter-storage group; n = 145). All units were leukoreduced prior to storage. All patients received 10 mL/kg of RBCs during hours 0 through 2 and, if indicated per protocol, an additional 10 mL/kg during hours 4 through 6.

MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients with a lactate level of 3 mmol/L or lower at 8 hours using a margin of noninferiority equal to an absolute difference of 25%. Secondary measures included noninvasive cerebral tissue oxygen saturation during the first transfusion, clinical and laboratory changes up to 24 hours, and survival and health at 30 days after transfusion. Adverse events were monitored up to 24 hours.

RESULTS: In the total population of 290 children, the mean (SD) presenting hemoglobin level was 3.7 g/dL (1.3) and mean lactate level was 9.3 mmol/L (3.4). Median (interquartile range) RBC unit storage was 8 days (7-9) for shorter storage vs 32 days (30-34) for longer storage without overlap. The proportion achieving the primary end point was 0.61 (95% CI, 0.52 to 0.69) in the longer-storage group vs 0.58 (95% CI, 0.49 to 0.66) in the shorter-storage group (between-group difference, 0.03 [95% CI, -0.07 to ∞], P < .001), meeting the prespecified margin of noninferiority. Mean lactate levels were not statistically different between the 2 groups at 0, 2, 4, 6, 8, or 24 hours. Kaplan-Meier analysis and global nonlinear regression revealed no statistical difference in lactate reduction between the 2 groups. Clinical assessment, cerebral oxygen saturation, electrolyte abnormalities, adverse events, survival, and 30-day recovery were also not significantly different between the groups.

CONCLUSIONS AND RELEVANCE: Among children with lactic acidosis due to severe anemia, transfusion of longer-storage compared with shorter-storage RBC units did not result in inferior reduction of elevated blood lactate levels. These findings have relevance regarding the efficacy of stored RBC transfusion for patients with critical tissue hypoxia and lactic acidosis due to anemia.

RBC Transfusion in Pediatric Patients Supported With Extracorporeal Membrane Oxygenation: Is There an Impact on Tissue Oxygenation? (Ruth)

Fiser RT, Irby K, Ward RM, et al. RBC Transfusion in Pediatric Patients Supported With Extracorporeal Membrane Oxygenation: Is There an Impact on Tissue Oxygenation?*. Pediatr Crit Care Med. 2014 Nov;15(9):806-13.

Full-text for Children’s and Emory users.

OBJECTIVE: To examine first the RBC transfusion practice in pediatric patients supported with extracorporeal membrane oxygenation and second the relationship between transfusion of RBCs and changes in mixed venous saturation (SvO2) and cerebral regional tissue oxygenation, as measured by near-infrared spectroscopy in patients supported with extracorporeal membrane oxygenation.

DESIGN: Retrospective observational study.

SETTING: Pediatric, cardiovascular, and neonatal ICUs of a tertiary care children’s hospital.

PATIENTS: All pediatric patients supported with extracorporeal membrane oxygenation between January 1, 2010, and December 31, 2010.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: There were 45 patients supported with extracorporeal membrane oxygenation. The median (interquartile range) phlebotomy during extracorporeal membrane oxygenation was 75 mL/kg (33, 149 mL/kg). A total of 617 transfusions were administered (median, 9 per patient; range = 1-57). RBC volumes transfused during extracorporeal membrane oxygenation support were 254 mL/kg (136, 557) and 267 mL/kg (187, 393; p = 0.82) for cardiac and noncardiac patients, respectively. Subtracting the volume of RBCs used for extracorporeal membrane oxygenation circuit priming, median RBC transfusion volumes were 131 and 80 mL/kg for cardiac and noncardiac patients, respectively (p = 0.26). The cardiac surgical patients received the most RBCs (529 vs 74 mL/kg for nonsurgical cardiac patients). The median hematocrit maintained during extracorporeal membrane oxygenation support was 37%, with no difference between cardiac and noncardiac patients. Patients supported with extracorporeal membrane oxygenation were exposed to a median of 10.9 (range, 3-43) individual donor RBC units. Most transfusions resulted in no significant change in either SvO2 or cerebral near-infrared spectroscopy. Only 5% of transfusions administered (31/617) resulted in an increase in SvO2 of more than 5%, whereas an increase in cerebral near-infrared spectroscopy of more than 5 was only observed in 9% of transfusions (53/617). Most transfusions (73%) were administered at a time when the pretransfusion SvO2 was more than 70%.

CONCLUSIONS: Patients supported with extracorporeal membrane oxygenation were exposed to large RBC transfusion volumes for treatment of mild anemia resulting from blood loss, particularly phlebotomy. In the majority of events, RBC transfusion did not significantly alter global tissue oxygenation, as assessed by changes in SvO2 and cerebral near-infrared spectroscopy. Most transfusions were administered at a time at which the patient did not appear to be oxygen delivery dependent according to global measures of tissue oxygenation.

Complications associated with prolonged hypertonic saline therapy in children with elevated intracranial pressure. (Krohn)

Pediatr Crit Care Med. 2013 Jul;14(6):610-20. PMID: 23823197

OBJECTIVES: Safe upper limits for therapeutic hypernatremia in the treatment of intracranial hypertension have not been well established. We investigated complications associated with hypernatremia in children who were treated with prolonged infusions of hypertonic saline.

DESIGN: Retrospective chart analysis.

SETTING: PICU in university-affiliated children’s hospital.

PATIENTS: All children from 2004 to 2009 requiring intracranial pressure monitoring (external ventricular drain or fiberoptic intraparenchymal monitor) for at least 4 days who were treated with hypertonic saline infusion for elevated intracranial pressure and did not meet exclusion criteria.

INTERVENTION: Continuous hypertonic saline infusion on a sliding scale was used to achieve target sodium levels that would keep intracranial pressure less than 20 mm Hg once the conventional therapies failed.

MEASUREMENTS AND MAIN RESULTS: Eighty-eight children met inclusion criteria. Etiologies of elevated intracranial pressure included trauma (n = 48), ischemic or hemorrhagic stroke (n = 20), infection (n = 8), acute disseminated encephalomyelitis (n = 5), neoplasm (n = 2), and others (n = 5). The mean peak serum sodium was 171.3 mEq/L (range, 150-202). The mean Glasgow Outcome Score was 2.8 (± 1.1) at time of discharge from the hospital. Overall mortality was 15.9%. Children with sustained (> 72 hr) serum sodium levels above 170 mEq/L had a significantly higher occurrence of thrombocytopenia (p < 0.001), renal failure (p < 0.001), neutropenia (p = 0.006), and acute respiratory distress syndrome (p = 0.029) after controlling for variables of age, gender, Pediatric Risk of Mortality score, duration of barbiturate-induced coma, duration of intracranial pressure monitoring, vasopressor requirements, and underlying pathology. Children with sustained serum sodium levels greater than 165 mEq/L had a significantly higher prevalence of anemia (p < 0.001).

CONCLUSIONS: Children treated by continuous hypertonic saline infusion for intracranial hypertension whose serum sodium levels exceeded certain thresholds experienced significantly more events of acute renal failure, thrombocytopenia, neutropenia, anemia, and acute respiratory distress syndrome than those whose sodium level was maintained below these thresholds.

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