The management of diabetic ketoacidosis in children

The object of this review is to provide the definitions, frequency, risk factors, pathophysiology, diagnostic considerations, and management recommendations for diabetic ketoacidosis (DKA) in children and adolescents, and to convey current knowledge of the causes of permanent disability or mortality from complications of DKA or its management, particularly the most common complication, cerebral edema (CE). DKA frequency at the time of diagnosis of pediatric diabetes is 10%–70%, varying with the availability of healthcare and the incidence of type 1 diabetes (T1D) in the community. Recurrent DKA rates are also dependent on medical services and socioeconomic circumstances. Management should be in centers with experience and where vital signs, neurologic status, and biochemistry can be monitored with sufficient frequency to prevent complications or, in the case of CE, to intervene rapidly with mannitol or hypertonic saline infusion. Fluid infusion should precede insulin administration (0.1 U/kg/h) by 1–2 hours; an initial bolus of 10–20 mL/kg 0.9% saline is followed by 0.45% saline calculated to supply maintenance and replace 5%–10% dehydration. Potassium (K) must be replaced early and sufficiently. Bicarbonate administration is contraindicated. The prevention of DKA at onset of diabetes requires an informed community and high index of suspicion; prevention of recurrent DKA, which is almost always due to insulin omission, necessitates a committed team effort

Efficacy and safety of dexanabinol in severe traumatic brain injury : results of a phase III randomised, placebo-controlled, clinical trial

Background Traumatic brain injury is a major cause of death and disability. We sought to assess the safety and efficacy of dexanabinol, a synthetic cannabinoid analogue devoid of psychotropic activity, in severe traumatic brain injury. Methods 861 patients with severe traumatic brain injury admitted to 86 specialist centres from 15 countries were included in a multi-centre, placebo-controlled, phase III trial. Patients were randomised to receive a single intravenous 150 mg dose of dexanabinol or placebo within 6 h of injury. The primary outcome was the extended Glasgow outcome scale assessed at 6 months, with the point of dichotomisation into unfavourable versus favourable outcome differentiated by baseline prognostic risk. Prespecified subgroup analyses were defined by injury severity, recruitment rate, and time to dosing. Secondary analysis included control of intracranial pressure and quality of life. Analysis were prespecified in the protocol and the statistical analysis plan. This study is registered with ClinicalTrials.gov, number NCT00129857. Findings 846 patients were included in the efficacy analysis. The extended Glasgow outcome scale at 6 months did not differ between groups; 215 (50%) patients in the dexanabinol group and 214 (51%) patients in the placebo group had an unfavourable outcome (odds ratio for a favourable response 1.04; 95% CI 0.79-1.36). Improvements in the control of intracranial pressure or quality of life were not recorded and subgroup analysis showed no indication of differential treatment effects. Dexanabinol was not associated with hepatic, renal, or cardiac toxic effects. Interpretation Dexanabinol is safe, but is not efficacious in the treatment of traumatic brain injury

How to manage refractory intracranial hypertension?

Intracranial hypertension is one of the major causes of secondary injury in traumatic brain injury leading to a significant burden of morbidity and mortality. We here present a review of available therapies for the treatment of refractory intracranial hypertension that is defined as an intracranial hypertension that does not respond to the firstline therapies. Second-line therapies that are available for the treatment of refractory intracranial hypertension include mild induced hypothermia, inotropes, and vasopressors for the control of cerebral perfusion pressure, transient hyperventilation, barbiturates, and decompressive craniectomy. Apart from decompressive craniectomy, these therapies are supported by the last guidelines published by the Brain Trauma Foundation (BTF). However, the level of evidence supporting them is low to moderate. This is probably partly explained by the fact that traumatic brain injury is extremely heterogeneous and requires multimodal and individualised care, which makes randomised clinical trials difficult to set up. On-going studies like those conducted on induced hypothermia (EUROTHERM3235) and on decompressive craniectomy (RESCUEicp) may lead to new perspectives for the management of patients suffering from refractory intracranial hypertension