Impact of hypernatremia on patients with severe traumatic brain injury

Abstract

IntroductionWe previously showed that erythropoietin (EPO) attenuates the morphological signs of spinal cord ischemia/reperfusion (I/R) injury in swine [1] without, however, improving neurological function. The clinical use of EPO has been cautioned most recently due to serious safety concerns arising from an increased mortality in acute stroke patients treated with EPO and simultaneously receiving systemic thrombolysis [2]. Carbamylated EPO (cEPO) is an EPO derivative without erythropoietic activity and devoid of the EPO side eff ects, but with apparently well maintained cytoprotective qualities [3]. We therefore tested the hypothesis whether cEPO may be equally effi cient as EPO in reducing morphological as well as functional aortic occlusion-induced spinal cord I/R injury. Methods In a randomized and blinded trial pigs received either vehicle (control, n = 9), EPO or cEPO, respectively (n = 9 each; 5,000 IU/kg over 30 minutes before and during the fi rst 4 hours of reperfusion). Animals underwent 30 minutes of thoracic aortic balloon occlusion with catheters placed immediately downstream of the A. subclavia and upstream of the aortic trifurcation. Spinal cord function was assessed by motor evoked potentials (MEP as percentage of the amplitude before aortic occlusion) and lower limb refl exes (assessed as the subjective strength of response) for a period of 10 hours after reperfusion. Tissue damage was evaluated using Nissl staining. Results Both EPO-treated and cEPO-treated animals presented with attenuated spinal cord injury in the Nissl staining (median (quartile) percentage of damaged neurons in the thoracic segments: control 27 (25,44), cEPO 8 (4,10), and EPO 5 (5,7), P <0.001 vs control group; in the lumbar segments: control 26 (19,32), cEPO 7 (5,13), EPO 8 (5,10), P <0.001 vs control group). However, while only cEPO treatment was associated with recovery of the MEP amplitude to pre-occlusion values when compared with the control group (P <0.05), lower limb refl ex response was comparably restored stronger in both treatment groups (P <0.05 vs control). Conclusions In a clinically relevant porcine model mimicking aortic crossclamping during vascular surgery repair of thoracic aortic aneurysm, cEPO protected spinal cord function and integrity as eff ective as EPO when applied at equipotent doses. Acknowledgements Supported by the Deutsche Forschungs gemeinschaft (SCHE 899/2-2). References Introduction Unfolded protein response (UPR)-mediated apoptosis plays a pivotal role in ischemia-reperfusion injury. Sodium 4-phenylbutyrate (PBA) has been reported to act as a chemical chaperone inhibiting UPR-mediated apoptosis triggered by ischemia in various organs other than the heart. Therefore we investigated whether PBA reduces UPR-mediated apoptosis and protects against myocardial ischemia-reperfusion injury in mice. Methods C57BL/6 mice were subjected to 30 minutes LAD ischemia followed by reperfusion. PBA (100 mg/kg) or PBS (control) was administrated intraperitoneally just before ischemia. Apoptosis, infarct ...

The effect of continuous hypertonic saline infusion and hypernatremia on mortality in patients with severe traumatic brain injury: a retrospective cohort study

“…32 Hypernatremia has itself been associated with elevated creatinine 33 and increased mortality 19,[34][35][36] in patients with brain injury. In 4,296 patients admitted to a neurocritical care unit (only 17% patients had a TBI), results of a retrospective cohort study showed that a Na level [ 160 mEqÁL -1 was independently associated with an increased ICU mortality (odds ratio [OR], 4.8; 95% CI, 2.4 to 9.6).…”

Morbidity and mortality associated with hypernatremia in patients with severe traumatic brain injury

“…10 Hypernatremia (≥ 150 mEq/L) is seen in 30%-40% of patients with TBI. 6,11,15,19 The etiology of hypernatremia may not be strictly defined in patients with TBI, and this condition may be due to hyperosmolar therapy; hypovolemia; insensible free water losses; or high sodium load in intravenous fluids, feeds, or medications. 20 Additionally, hypothalamic dysfunction not resulting in overt diabetes insipidus may contribute to hypernatremia after TBI.…”

Associação de hipernatremia com o prognóstico e a mortalidade de pacientes com traumatismo cranioencefálico grave em um hospital terciário brasileiro

“…Também em 2009, Maggiore et al (71) (71) Em 2010, Shehata et al (142) apresentaram hiponatremia e 20 (25%), hipernatremia (143) . A incidência das disnatremias entre os pacientes com lesões difusas foi maior do que entre aqueles que tiveram hematoma intracerebral (p = 0,022).…”

“…(20,23) Também por motivos de maior exposição a situações de risco (imprudência no trânsito, incluindo o consumo de bebidas alcoólicas antes da condução; trabalhos fora de casa; uso de drogas ilícitas e envolvimento em contextos de violência e agressões físicas, entre outros), a população jovem também é a mais prevalente em estudos clínicos e epidemiológicos sobre o TCE. (1,20,146) Na revisão brasileira conduzida por Magalhães et al (20) , (7,71,72,140,142,144) Um pouco mais da metade dos pacientes avaliados neste estudo foi procedente de trabalho, foram considerados todos os traumas e não apenas o TCE. (29) No nosso estudo, os acidentes de trânsito foram os principais causadores de TCE na população estudada, compreendendo 76,7% de todas as causas, similarmente ao visto em outros estudos brasileiros e de outras regiões do mundo.…”

“…[3][4][5][6][7][8]. (71,72,144,151) Apesar da alta gravidade revelada pelos índices de trauma em nosso estudo, quase 90% (142,148) Na terceira edição das diretrizes para o manejo de pacientes com TCE grave da BTF publicada em 2007, recomendava-se a monitorização da PIC em todos os pacientes com TCE grave e presença, na tomografia de crânio inicial, de edema, hematomas, contusão, herniação ou compressão de cisternas, com nível II de evidência. (152) Na quarta edição das diretrizes, publicada em 2016, esta recomendação foi citada, porém com a consideração de que não há evidências robustas que a suportem; entretanto, a orientação de usar monitorização da PIC no manejo de pacientes com TCE grave com risco para HIC, com o objetivo de reduzir a mortalidade em 14 dias está presente nesta diretriz, com nível IIB de evidência.…”