Ketamine for critically ill patients with severe acute brain injury: Protocol for a systematic review with meta-analysis and Trial Sequential Analysis of randomised clinical trials.

INTRODUCTION: Intensive care for patients with severe acute brain injury aims both to treat the immediate consequences of the injury and to prevent and treat secondary brain injury to ensure a good functional outcome. Sedation may be used to facilitate mechanical ventilation, for treating agitation, and for controlling intracranial pressure. Ketamine is an N-methyl-D-aspartate receptor antagonist with sedative, analgesic, and potentially neuroprotective properties. We describe a protocol for a systematic review of randomised clinical trials assessing the beneficial and harmful effects of ketamine for patients with severe acute brain injury. METHODS AND ANALYSIS: We will systematically search international databases for randomised clinical trials, including CENTRAL, MEDLINE, Embase, and trial registries. Two authors will independently review and select trials for inclusion, and extract data. We will compare ketamine by any regimen versus placebo, no intervention, or other sedatives or analgesics for patients with severe acute brain injury. The primary outcomes will be functional outcome at maximal follow up, quality of life, and serious adverse events. We will also assess secondary and exploratory outcomes. The extracted data will be analysed using Review Manager and Trials Sequential Analysis. Evidence certainty will be graded using GRADE. ETHICS AND DISSEMINATION: The results of the systematic review will be disseminated through peer-reviewed publication. With the review, we hope to inform future randomised clinical trials and improve clinical practice. PROSPERO NO: CRD42021210447.

Timing of intraventricular infusion test for diagnosing idiopathic normal pressure hydrocephalus.

BACKGROUND: Infusion tests, which measure resistance to outflow (Rout), are used in selecting patients suspected for idiopathic normal pressure hydrocephalus (iNPH) for shunt surgery. Infusion tests can be performed through an external ventricular drain (EVD). A 24-hour time gap from EVD insertion to an infusion test is a routine practice at our department due to concerns that the surgical procedure might influence the test results in the immediate postoperative period. The objective of the study was to investigate if timing of an intraventricular infusion test influences the results of the test in patients suspected for iNPH. METHODS: Ten patients scheduled for an intraventricular infusion test were included. Measurements of baseline intracranial pressure (ICP) and plateau ICP were obtained during constant rate intraventricular infusion test performed at two time points (1 and 24 h after EVD insertion) and Rout was calculated from these measures and compared within patients. RESULTS: Eight patients completed both infusion tests. In one of the 18 infusion tests performed, it was not possible to define an ICP plateau and this infusion test was excluded, leaving 7 paired infusion tests. Median Rout was 12.9 mmHg/ml/min (range 7.0-22.0) 1 h after EVD insertion and 11.3 mmHg/ml/min (range 7.8-18.1) after 24 h. Overall, there were no statistically significant differences in Rout (P = 0.83), baseline ICP (P = 0.70), or plateau ICP (P = 0.81) between the recordings performed 1 h and 24 h after EVD insertion. For two of the seven patients with paired infusion tests, there was poor agreement between Rout values at 1 and 24 h. CONCLUSION: Overall, Rout estimates do not change significantly between 1 and 24 h after EVD insertion. We therefore propose that infusion tests can be performed shortly after surgery to reduce the period of indwelling EVD and duration of hospitalization.

Long-Term Effect of Decompressive Craniectomy on Intracranial Pressure and Possible Implications for Intracranial Fluid Movements.

BACKGROUND: Decompressive craniectomy (DC) is used in cases of severe intracranial hypertension or impending intracranial herniation. DC effectively lowers intracranial pressure (ICP) but carries a risk of severe complications related to abnormal ICP and/or cerebrospinal fluid (CSF) circulation, eg, hygroma formation, hydrocephalus, and "syndrome of the trephined." OBJECTIVE: To study the long-term effect of DC on ICP, postural ICP regulation, and intracranial pulse wave amplitude (PWA). METHODS: Prospective observational study including patients undergoing DC during a 12-mo period. Telemetric ICP sensors (Neurovent-P-tel; Raumedic, Helmbrechts, Germany) were implanted in all patients. Following discharge from the neuro intensive care unit (NICU), scheduled weekly ICP monitoring sessions were performed during the rehabilitation phase. RESULTS: A total of 16 patients (traumatic brain injury: 7, stroke: 9) were included (median age: 55 yr, range: 19-71 yr). Median time from NICU discharge to cranioplasty was 48 d (range: 16-98 d) and during this period, mean ICP gradually decreased from 7.8 ± 2.0 mm Hg to -1.8 ± 3.3 mm Hg (P = .02). The most pronounced decrease occurred during the first month. Normal postural ICP change was abolished after DC for the entire follow-up period, ie, there was no difference between ICP in supine and sitting position (P = .67). PWA was markedly reduced and decreased from initially 1.2 ± 0.7 mm Hg to 0.4 ± 0.3 mm Hg (P = .05). CONCLUSION: Following NICU discharge, ICP decreases to negative values within 4 wk, normal postural ICP regulation is lost and intracranial PWA is diminished significantly. These abnormalities might have implications for intracranial fluid movements (eg, CSF and/or glymphatic flow) following DC and warrants further investigations.

Intracranial pressure before and after cranioplasty: insights into intracranial physiology.

OBJECTIVE: Decompressive craniectomy (DC) is an emergency neurosurgical procedure used in cases of severe intracranial hypertension or impending intracranial herniation. The procedure is often lifesaving, but it exposes the brain to atmospheric pressure in the subsequent rehabilitation period, which changes intracranial physiology and probably leads to complications such as hydrocephalus, hygromas, and "syndrome of the trephined." The objective of the study was to study the effect of cranioplasty on intracranial pressure (ICP), postural ICP changes, and intracranial pulse wave amplitude (PWA). METHODS: The authors performed a prospective observational study including patients who underwent DC during a 12-month period. Telemetric ICP sensors were implanted in all patients at the time of DC. ICP was evaluated before and after cranioplasty during weekly measurement sessions including a standardized postural change program. RESULTS: Twelve of the 17 patients enrolled in the study had cranioplasty performed and were included in the present investigation. Their mean ICP in the supine position increased from -0.5 ± 4.8 mm Hg the week before cranioplasty to 6.3 ± 2.5 mm Hg the week after cranioplasty (p < 0.0001), whereas the mean ICP in the sitting position was unchanged (-1.2 ± 4.8 vs -1.1 ± 3.6 mm Hg, p = 0.90). The difference in ICP between the supine and sitting positions was minimal before cranioplasty (1.1 ± 1.8 mm Hg) and increased to 7.4 ± 3.6 mm Hg in the week following cranioplasty (p < 0.0001). During the succeeding 2 weeks of the follow-up period, the mean ICP in the supine and sitting positions decreased in parallel to, respectively, 4.6 ± 3.0 mm Hg (p = 0.0003) and -3.9 ± 2.7 mm Hg (p = 0.040), meaning that the postural ICP difference remained constant at around 8 mm Hg. The mean intracranial PWA increased from 0.7 ± 0.7 mm Hg to 2.9 ± 0.8 mm Hg after cranioplasty (p < 0.0001) and remained around 3 mm Hg throughout the following weeks. CONCLUSIONS: Cranioplasty restores normal intracranial physiology regarding postural ICP changes and intracranial PWA. These findings complement those of previous investigations on cerebral blood flow and cerebral metabolism in patients after decompressive craniectomy.

Valved or valveless ventriculoperitoneal shunting in the treatment of post-haemorrhagic hydrocephalus: a population-based consecutive cohort study.

BACKGROUND: Implant infection and obstruction are major complications for ventriculoperitoneal shunts in patients with post-haemorrhagic hydrocephalus. In an effort to (1) reduce the incidence of these complications, (2) reduce the rate of shunt failure and (3) shorten the duration of neurosurgical hospitalisation, we have implemented valveless ventriculoperitoneal shunts at our department for adult patients with post-haemorrhagic hydrocephalus and haemorrhagic cerebrospinal fluid at the time of shunt insertion. METHODS: All adult patients (>18 years old) treated for post-haemorrhagic hydrocephalus with ventriculoperitoneal shunting at our institution from 1 January 2008 to 31 December 2014 were included in this retrospective population-based consecutive cohort study. Data were collected by retrospectively reviewing medical records. We compared two different shunt modalities (valveless vs valve-regulated), analysing frequencies of complications, shunt survival and duration of neurosurgical hospitalisation. RESULTS: A total of 214 patients aged 22-86 (mean age, 60.5 ± 11.5 years) were included, comprising 137 valveless and 77 valve-regulated shunts. We found no difference in the rate of surgical shunt revision (p = 0.65) or differences in time interval from insertion to first surgical revision (p = 0.31) between the two shunt modalities. The duration of neurosurgical hospitalisation was shorter for patients receiving a valveless shunt (p = 0.004). Patients with valveless shunts had a lower rate of shunt infection (5.1 % vs 14.3 %, p = 0.02), but a higher rate of overdrainage (10.3 % vs 2.6 %, p = 0.04). CONCLUSION: The use of a valveless shunting for patients with post-haemorrhagic hydrocephalus results in shorter duration of neurosurgical hospitalisation and lower rate of shunt infection, although these advantages should be held up against the risk of overdrainage. We propose valveless shunting to be used as first-line shunting strategy in this patient category, with careful follow-up ensuring that these are substituted by a valve-bearing system if necessary.