Development and External Validation of a Machine Learning Model for the Early Prediction of Doses of Harmful Intracranial Pressure in Patients with Severe Traumatic Brain Injury.

Treatment and prevention of elevated intracranial pressure (ICP) is crucial in patients with severe traumatic brain injury (TBI). Elevated ICP is associated with secondary brain injury, and both intensity and duration of an episode of intracranial hypertension, often referred to as "ICP dose," are associated with worse outcomes. Prediction of such harmful episodes of ICP dose could allow for a more proactive and preventive management of TBI, with potential implications on patients' outcomes. The goal of this study was to develop and validate a machine-learning (ML) model to predict potentially harmful ICP doses in patients with severe TBI. The prediction target was defined based on previous studies and included a broad range of doses of elevated ICP that have been associated with poor long-term neurological outcomes. The ML models were used, with minute-by-minute ICP and mean arterial blood pressure signals as inputs. Harmful ICP episodes were predicted with a 30 min forewarning. Models were developed in a multi-center dataset of 290 adult patients with severe TBI and externally validated on 264 patients from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) dataset. The external validation of the prediction model on the CENTER-TBI dataset demonstrated good discrimination and calibration (area under the curve: 0.94, accuracy: 0.89, precision: 0.87, sensitivity: 0.78, specificity: 0.94, calibration-in-the-large: 0.03, calibration slope: 0.93). The proposed prediction model provides accurate and timely predictions of harmful doses of ICP on the development and external validation dataset. A future interventional study is needed to assess whether early intervention on the basis of ICP dose predictions will result in improved outcomes.

Controlled Decompression Alleviates Brain Injury via Attenuating Oxidative Damage and Neuroinflammation in Acute Intracranial Hypertension.

BACKGROUND: The benefits of controlled decompression (CDC) for patients with acute intracranial hypertension especially in terms of alleviating the complications caused by rapid decompression (RDC) have been confirmed by clinical studies. This study is aimed at evaluating the therapeutic potency of CDC with ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) by investigating the potential molecular mechanism in the acute intracranial hypertension (AICH) rabbit model. METHODS: Male New Zealand white rabbits were randomly subdivided into the sham-operated (SH) group, CDC group, and RDC group. Blood plasma samples and brain tissue were collected 2 days before operation (baseline) and at 3, 6, 24, and 72 hours after operation to measure the levels of UCH-L1, GFAP, oxidative stress indicators, and inflammatory cytokines by performing ELISA or Western blot. The neurological score of the rabbits and brain water content was graded 24 h after surgery. qPCR, immunofluorescence, and FJ-C staining were conducted. RESULTS: CDC improved neurological function, lowered brain water content, ameliorated neuronal degeneration, attenuated oxidative damage, and inflammatory responses to a greater extent than RDC. Plasma UCH-L1 level was significantly lower in the CDC group at 3 h postoperatively than in the RDC group. CDC reduced plasma GFAP levels to various degrees at 3 h, 6 h, and 24 h postoperatively compared with RDC. Immunofluorescence confirmed that the expression of UCH-L1 and GFAP in the cortex of the CDC group was lower than that of the RDC group. CONCLUSIONS: Our data collectively demonstrate that CDC could attenuate oxidative damage and inflammatory responses, downregulate UCH-L1 and GFAP levels, and contribute to an improved neuroprotective effect compared with RDC.

Short-duration hypothermia completed prior to reperfusion prevents intracranial pressure elevation following ischaemic stroke in rats.

Reperfusion therapies re-establish blood flow after arterial occlusion and improve outcome for ischaemic stroke patients. Intracranial pressure (ICP) elevation occurs 18-24 h after experimental stroke. This elevation is prevented by short-duration hypothermia spanning the time of reperfusion. We aimed to determine whether hypothermia-rewarming completed prior to reperfusion, also prevents ICP elevation 24 h post-stroke. Transient middle cerebral artery occlusion was performed on male outbred Wistar rats. Sixty-minute hypothermia to 33 °C, followed by rewarming was induced prior to reperfusion in one group, and after reperfusion in another group. Normothermia controls received identical anaesthesia protocols. ΔICP from pre-stroke to 24 h post-stroke was measured, and infarct volumes were calculated. Rewarming pre-reperfusion prevented ICP elevation (ΔICP = 0.3 ± 3.9 mmHg vs. normothermia ΔICP = 5.2 ± 2.1 mmHg, p = 0.02) and reduced infarct volume (pre-reperfusion = 78.6 ± 23.7 mm3 vs. normothermia = 125.1 ± 44.3 mm3, p = 0.04) 24 h post-stroke. There were no significant differences in ΔICP or infarct volumes between hypothermia groups rewarmed pre- or post-reperfusion. Hypothermia during reperfusion is not necessary for prevention of ICP rise or infarct volume reduction. Short-duration hypothermia may be an applicable early treatment strategy for stroke patients prior to- during-, and after reperfusion therapy.

Efficacy of a Novel Prophylactic Barbiturate Therapy for Severe Traumatic Brain Injuries: Step-down Infusion of a Barbiturate with Normothermia.

This study aimed to examine the beneficial effects of a novel prophylactic barbiturate therapy, step-down infusion of barbiturates, using thiamylal with normothermia (NOR+sdB), on the poor outcome in the patients with severe traumatic brain injuries (sTBI), in comparison with mild hypothermia (MD-HYPO). From January 2000 to March 2019, 4133 patients with TBI were admitted to our hospital. The inclusion criteria were: a Glasgow coma scale (GCS) score of ≤8 on admission, age between 20 and 80 years, intracranial hematoma requiring surgical evacuation of the hematoma with craniotomy and/or external decompression, and patients who underwent management of body temperature and assessed their outcome at 6-12 months. Finally, 43 patients were included in the MD-HYPO (n = 29) and NOR+sdB (n = 14) groups. sdB was initiated intraoperatively or immediately after the surgical treatment. There were no significant differences in patient characteristics, including age, sex, past medical history, GCS on admission, type of intracranial hematoma, and length of hospitalization between the two groups. Although NOR+sdB could not improve the patient's poor outcome either at discharge from the intensive care unit (ICU) or at 6-12 months after admission, the treatment inhibited composite death at discharge from the ICU. The mean value of the maximum intracranial pressure (ICP) in the NOR+sdB group was <20 mmHg throughout the first 120 h. NOR+sdB prevented composite death in the ICU in patients with sTBI, and we may obtain novel insights into the beneficial role of prophylactic barbiturate therapy from suppression of the elevated ICP during the first 120 h.

Failure of an effective physiologic threshold compliance tool to demonstrate benefit in a clinical trial of traumatic brain injury patients.

BACKGROUND: Better physiologic threshold compliance holds promise for improving outcomes in neurocritical care patients. METHODS: Our group developed a threshold compliance tool. This software computes and displays the proportion of values out of range in real time. We captured intracranial pressure (ICP) measures in our patients before and after implementation of this technology. Ten months after the threshold compliance tool was introduced we initiated a randomized controlled trial involving acute traumatic brain injury (TBI) patients to assess whether the tool was effective at reducing out-of-range ICP values. RESULTS: A total of 54 patients with ICP monitors were included in our analysis, 42 of whom sustained a TBI. Implementation of the threshold compliance tool was associated with an 85.3% reduction in ICP values exceeding 22 mmHg in neurocritical care patients (p = 0.004) and a 76.8% reduction in patients with TBI (p = 0.043). Out-of-range values in an area-under-the-curve analysis were reduced by 78.8% in all patients (p = 0.009) and in TBI patients by 77.9% (p = 0.051). Out-of-range values were not further reduced during our randomized controlled trial examining the threshold compliance tool, and a difference between treatment groups was not suggested. CONCLUSIONS: Implementation of a threshold compliance tool was associated with a marked and significant reduction in out-of-range ICP values. Benefit was, however, not evident in a randomized controlled trial. Our analysis provides a unique perspective on our failure to detect an apparent true difference and may provide insights into other neurotrauma trial failures.

Effects of Primary Decompressive Craniectomy on the Outcomes of Serious Traumatic Brain Injury with Mass Lesions, and Independent Predictors of Operation Decision.

BACKGROUND: Although operative indications for traumatic brain injury (TBI) are known, neurosurgeons are unsure whether to remove the bone flap after mass lesion extraction, and an efficient scoring system for predicting which patients should undergo decompressive craniectomy (DC) does not exist. METHODS: Nine parameters were assessed. In total, 245 patients with severe TBI were retrospectively assessed from June 2015 to May 2019, who underwent DC or craniotomy to remove mass lesions. The 6-month mortality and Extended Glasgow Outcome Scale scores were compared between the DC and craniotomy groups. Using univariable and multivariable logistic regression equations, receiver operating characteristic curves were obtained for predicting the decision for DC. RESULTS: The overall 6-month mortality in the entire cohort was 11.43% (28/245). Patients undergoing DC had lower mean preoperative Glasgow Coma Scale scores (P = 0.01), and higher amounts of individuals with a Glasgow Coma Scale score of 6 (P = 0.007), unresponsive pupillary light reflex (P < 0.001), closed basal cisterns (P < 0.001), and diffuse injury (P = 0.025), compared with the craniotomy group. Because of high disease severity, individuals administered primary DC showed increased 6-month mortality compared with the craniotomy group. However, in surviving patients, favorable Extended Glasgow Outcome Scale rates were similar in both groups. Pupillary light reflex and basal cisterns were independent predictors of the DC decision. Based on receiver operating characteristic curves, the model had sensitivity and specificity of 81.6% and 84.9%, respectively, in predicting the probability of DC. CONCLUSIONS: These preliminary data showed that primary DC may benefit some patients with severe TBI with mass lesions. In addition, unresponsive preoperative pupil reaction and closed basal cistern could predict the DC decision.

Putting 'CSF-Shift Edema' Hypothesis to Test: Comparing Cisternal and Parenchymal Pressures After Basal Cisternostomy for Head Injury.

BACKGROUND: Increased brain edema in head injury is due to shift of cerebrospinal fluid (CSF) from cisterns at high pressure to brain parenchyma at low pressure. By opening basal cisterns and decreasing the increased cisternal pressure, basal cisternostomy (BC) results in reversal of CSF shift from parenchyma to cisterns, leading to decreased brain edema. Though the CSF-shift edema hypothesis is based on pressure difference between cisterns and brain parenchyma, the relationship of these pressures has not been studied. METHODS: A prospective clinical study was conducted from November 2018 to March 2020 including adult patients with head injury who were candidates for standard decompressive hemicraniectomy (DHC). All patients had neurological assessment and head computed tomography preoperatively and postoperatively. All patients underwent BC with DHC. Postoperatively, parenchymal and cisternal pressures and neurological condition were monitored hourly for 72 hours. RESULTS: Nine (5 men, 4 women) patients with head injury (mean age, 45.7 years; range, 25-72 years) underwent DHC-BC. Median Glasgow Coma Scale score of patients at admission was 8 (range, 4-14), and median midline shift on computed tomography was 8 mm (range, 7-12 mm). There was a significant difference between opening (25.70 ± 10.48 mm Hg) and closing (11.30 ± 5.95 mm Hg) parenchymal pressures (t9 = 3.963, P = 0.003). Immediate postoperative cisternal pressure was 1-11 mm Hg and was lower than immediate postoperative parenchymal pressure in all except 1 patient. Postoperatively, if cisternal pressure remained low, parenchymal pressure also decreased, and patients showed clinical improvement. Patients showing increased cisternal pressure showed increased parenchymal pressure and clinical worsening. CONCLUSIONS: Our study supports the CSF-shift edema hypothesis. Following DHC-BC, cisternal pressure is lowered to near-atmospheric pressure, and its relationship to parenchymal pressure predicts the future course of patients by reversal or re-reversal of CSF shift.

Sonographic Optic Nerve Sheath Diameter Following Seizure Prophylaxis in Pre-Eclamptic Parturients With Severe Features: A Prospective, Observational Study.

OBJECTIVES: Neurological manifestations, including raised intracranial pressures, are a hallmark of worsening pre-eclampsia. Invasive methods for measuring intracranial pressure, though a gold standard, are not always a viable option. Maternal ocular sonography is a promising bedside tool, which serves as a noninvasive, cost-effective means for measuring optic nerve sheath diameter (ONSD), a surrogate marker of raised intracranial pressures. We studied the ultrasonographically measured ONSD in severely pre-eclamptic women, and the effect of magnesium sulfate therapy on its values. METHODS: Thirty severely pre-eclamptic women at ≥28 weeks gestation were included. We recorded baseline ONSD values, serum magnesium levels, neurological symptoms, vitals, and repeated them at 4 and 12 hours following magnesium sulfate therapy, and then at 24 hours postpartum. An ONSD value >5.8 mm was suggestive of raised intracranial pressure. Primary outcome measure was to evaluate changes in ultrasonographically measured ONSD following seizure prophylaxis with magnesium sulfate. RESULTS: Women, 73.3%, had baseline ONSD >5.8 mm, with mean diameter being significantly high (6.02 ± 0.77 mm). There was a statistically nonsignificant decline in mean ONSD values at 4 and 12 hours, as well as at 24 hours postpartum. Patients with neurological symptoms declined significantly (from 70 to 10%; p value <.001) following magnesium sulfate therapy. CONCLUSIONS: Majority of severely pre-eclamptic parturients had high ONSD value suggestive of raised intracranial pressures, which persisted in the postpartum period and was unaffected by magnesium sulfate therapy. Ultrasound can thus serve as a point-of-care, cost-effective, easily available bedside tool for indirectly measuring intracranial pressures in this high-risk population.

Saethre-Chotzen syndrome: long-term outcome of a syndrome-specific management protocol.

AIM: To assess the long-term outcomes of our management protocol for Saethre-Chotzen syndrome, which includes one-stage fronto-orbital advancement. METHOD: All patients born with Saethre-Chotzen syndrome between January 1992 and March 2017 were included. Evaluated parameters included occipital frontal head circumference (OFC), fundoscopy, neuroimaging (ventricular size, tonsillar position, and the presence of collaterals/an abnormal transverse sinus), polysomnography, and ophthalmological outcomes. The relationship between papilledema and its associated risk factors was evaluated with Fisher's exact test. RESULTS: Thirty-two patients (21 females, 11 males) were included. Median (SD) age at first surgery was 9.6 months (3.1mo) for patients who were primarily referred to our center (range: 3.6-13.0mo), the median (SD) age at last follow-up was 13 years (5y 7mo; range: 3-25y). Seven patients had papilledema preoperatively, which recurred in two. Two patients had papilledema solely after first surgery. Second cranial vault expansion was indicated in 20%. Thirteen patients had an OFC deflection, indicating restricted skull growth, one patient had ventriculomegaly, and none developed hydrocephalus. Eleven patients had emissary veins, while the transverse sinus was aberrant unilaterally in 13 (hypoplastic n=10 and absent n=3). Four patients had mild tonsillar descent, one of which was a Chiari type I malformation. Four patients had obstructive sleep apnoea (two mild, one moderate, and one severe). An aberrant transverse sinus was associated with papilledema (p=0.01). INTERPRETATION: Single one-stage fronto-orbital advancement was sufficient to prevent intracranial hypertension for 80% of our patients with Saethre-Chotzen syndrome. Follow-up should focus on OFC deflection and venous anomalies.

The effect of laryngoscope types on hemodynamic response and optic nerve sheath diameter. McCoy, Macintosh, and C-MAC video-laryngoscope.

OBJECTIVES: This study aims to investigate the effect of McCoy, Macintosh laryngoscope, and C-MAC video-laryngoscopes on optic nerve sheath diameter (ONSD) and hemodynamic responses to laryngoscopy and intubation. METHODS: This prospective randomized study was conducted in Zonguldak Bülent Ecevit University Hospital, Zonguldak, Turkey, between July 2019 and January 2020. Informed written consent was obtained from all patients. Patients with previous intracranial/ocular surgery or glaucoma were excluded from the study. The patients were randomized to use McCoy, Macintosh, and C-MAC (30 per group). Intubations were performed by the same person. Mean arterial pressure, heart rate (HR), and ONSD were recorded before the induction and repeated in 1, 3, 5, and 10 minutes after the intubation. RESULTS: The effects of laryngoscopy and intubation on hemodynamic responses and ONSD were similar between groups (p greater than 0.05). While the comparison within groups showed ONSD increase in McCoy group and HR and ONSD increase in the Macintosh group compared to baseline 1 min after the intubation, no change was observed in hemodynamic responses and ONSD measurements in the C-MAC® group (p greater than 0.05). CONCLUSIONS: In this study, there was no significant difference between the groups in terms of ONSD and hemodynamic responses to laryngoscopy and intubation. It was observed that there were no significant changes in ONSD values just in C-MAC® video-laryngoscope group. Therefore, intubations with C-MAC® video-laryngoscope are thought to be more appropriate for patients with an increase in intracranial pressure.

Intracranial Hypertension and Intra-abdominal Pressure. Is it Worth Measuring?

Patients with refractory intracranial hypertension who have already undergone all the measures recommended by the current guidelines can benefit from having their intraabdominal pressure monitored since its increase generates hemodynamic repercussions and secondary elevation of intracranial pressure. In this context, a bibliographic research was performed on PubMed with the terms intra-abdominal pressure, abdominal compartment syndrome, intracranial pressure, intracranial hypertension. Altogether, 146 articles were observed, 87 of which were from the year 2000, and only 15 articles were considered relevant to the topic. These studies indicate that patients with refractory intracranial hypertension can benefit fromthe measurement of intraabdominal pressure, since there is evidence that an increase in this pressure leads to organic dysfunctions with an indirect impact on cerebral venous return and, consequently, an increase in intracranial pressure. In thosewho underwent decompression laparotomy, direct effectswere observed in reducing intracranial hypertension and survival.

How I do it: flexible endoscopic aspiration of intraventricular hemorrhage.

BACKGROUND: As intraventricular blood is a strong negative prognostic factor, intraventricular hemorrhage requires prompt and aggressive management to reduce intracranial hypertension. METHOD: A flexible scope can be used to navigate and to aspirate blood clots from all four ventricles. Complete restoration of CSF pathways from the lateral ventricle to the foramen of Magendie can be obtained. CONCLUSION: Flexible neuroendoscopic aspiration of IVH offers the opportunity to immediately reduce intracranial hypertension, reduce EVD obstruction and replacement rates, and decrease infections and shunt dependency.

Antipsychotic pitfalls: idiopathic intracranial hypertension and antipsychotic-induced weight gain.

Idiopathic intracranial hypertension (IIH) is a condition associated with poor vision and headaches that can cause disability and reduced quality of life. The onset of IIH is typically associated with sudden weight gain and obesity, which may be due to first-generation or second-generation antipsychotics. This case involved the use of quetiapine in an obese, 28-year-old woman; she gained significant weight after starting the antipsychotic and later developed headaches and blurred vision. Reducing quetiapine and administering acetazolamide significantly improved her symptoms within 4 weeks. This case reminds physicians to consider IIH as a cause of headache and vision loss in patients who have gained weight after starting or increasing quetiapine.

Discrepancy Between Internal and External Intracranial Pressure Transducers: Quantification of an Old Source of Error in EVDs?

BACKGROUND: Intracranial pressure monitoring remains the foundation for prevention of secondary injury after traumatic brain injury and is most commonly performed using an external ventricular drain or intraparenchymal pressure monitor. The Integra Flex ventricular catheter combines an external ventricular catheter with a pressure transducer embedded in the tip of the catheter to allow continuous pressure readings while simultaneously draining cerebrospinal fluid. Discrepancies between measurements from the continuously reported internal pressure transducer and intermittently assessed and externally transduced ventricular drain prompted an analysis and characterization of pressures transduced from the same ventricular source. METHODS: More than 500 hours of high-resolution (125 Hz) continuous recordings were manually reviewed to identify 73 hours of simultaneous measurements (clamped external ventricular drain) from internal and external transducers in patients with traumatic brain injury. RESULTS: A significant positive bias was found in pressure readings obtained from external relative to internal measurements. The 2 methods of measurement generally correlated poorly with each other and variably. Although proportional bias was found with Bland-Altman analysis, coherence revealed rare shifts in the external transducer as a major source of discrepancy. Infrequent changes in the 0-level of the external transducer were found to be the primary source of discrepancy. Relative to the observed differences, no significant trend was observed over time between the 2 modalities. CONCLUSIONS: This study suggests that the internal pressure transducer may be a more reliable estimate of intracranial pressure relative to bedside external transducers due to the inherent behavioral requirement of leveling.

A Comparative Analysis Between Four-Quadrant Osteoplastic Decompressive Craniotomy versus Conventional Decompressive Craniectomy for Traumatic Brain Injury.

OBJECTIVE: Primary decompressive craniectomy (DC) is indicated to evacuate the hematoma and reduce intracranial pressure in traumatic brain injury (TBI). However, there are a myriad of complications because of absence of the bone flap. A novel technique, four-quadrant osteoplastic decompressive craniotomy (FoQOsD) retains the bone flap while achieving adequate cerebral decompression. METHODS: A single-center randomized controlled trial of 115 patients with TBI needing decompressive surgery was conducted. Of these patients, 59 underwent DC and 56 underwent FoQOsD. The primary outcome determined was functional status at 6 months using the Glasgow Outcome Scale-Extended. RESULTS: No significant differences were identified in baseline characteristics between both groups. Mean Glasgow Outcome Scale-Extended score was comparable at 6 months (4.28 in DC vs. 4.38 in FoQOsD; P = 0.856). Further, 22 of 58 patients in the DC group had died (38%) compared with 25 of 55 patients in the FoQOsD group (44.6%) (odds ratio [OR], 1.19; 95% confidence interval [CI], 0.6-2.36; P = 0.6) (1 patient lost to follow-up in each group). A favorable outcome was seen in 56.8% of patients in the DC group versus 54.4% of patients in the FoQOsD group (P = 0.74). Presence of intraventricular hemorrhage and subarachnoid hemorrhage (OR, 7.17; 95% CI, 1.364-37.7; P = 0.020), opposite side contusions (OR, 3.838; 95% CI, 1.614-9.131; P = 0.002) and anisocoria (OR, 3.235; 95% CI, 1.490-7.026; P = 0.003) preoperatively were individual factors that played a significant role in final outcome. CONCLUSIONS: FoQOsD is as efficacious as conventional DC with the added benefit of avoiding a second surgery. The procedure is associated with better cosmesis and fewer complications.

Dexmedetomidine attenuates the increase of ultrasonographic optic nerve sheath diameter as a surrogate for intracranial pressure in patients undergoing robot-assisted laparoscopic prostatectomy: A randomized double-blind controlled trial.

BACKGROUND: Pneumoperitoneum and steep Trendelenburg position during robot-assisted laparoscopic prostatectomy (RALP) can increase intracranial pressure (ICP). Dexmedetomidine, a highly selective alpha-2 adrenergic receptor agonist, can cause cerebral vasoconstriction and decrease cerebral blood flow by stimulating the postsynaptic alpha-2 adrenergic receptors on cerebral blood vessels. However, the effects of dexmedetomidine on ICP are controversial and have not been evaluated during RALP under the establishment of pneumoperitoneum in the steep Trendelenburg position. Therefore, we evaluated the effect of dexmedetomidine on optic nerve sheath diameter (ONSD) as a surrogate for assessing ICP during RALP. METHODS: Patients were randomly allocated to receive dexmedetomidine (n = 63) (loading dose, 1 µg/kg for 10 minutes and continuous infusion, 0.4 µg/kg/hr) or normal saline (n = 63). The ONSD was measured at 10 minutes after induction of anesthesia in the supine position (T1), 30 minutes (T2) and 60 minutes (T3) after establishment of pneumoperitoneum in the steep Trendelenburg position, and at closing the skin in the supine position (T4). Hemodynamic and respiratory variables were measured at every time point. RESULTS: ONSDs at T2, T3, and T4 were significantly smaller in the dexmedetomidine group than in the control group (5.26 ±â€Š0.25 mm vs 5.71 ±â€Š0.26 mm, 5.29 ±â€Š0.24 mm vs 5.81 ±â€Š0.23 mm, and 4.97 ±â€Š0.24 mm vs 5.15 ±â€Š0.28 mm, all P <.001). ONSDs at T2, T3, and T4 were significantly increased compared to T1 in both groups. Hemodynamic and respiratory variables, except heart rate, did not significantly differ between the 2 groups. The bradycardia and atropine administration were not significantly different between the 2 groups. CONCLUSION: Dexmedetomidine attenuates the increase of ONSD during RALP, suggesting that intraoperative dexmedetomidine administration may effectively attenuate the ICP increase during pneumoperitoneum in the Trendelenburg position.

Lowering blood pressure after acute intracerebral haemorrhage: protocol for a systematic review and meta-analysis using individual patient data from randomised controlled trials participating in the Blood Pressure in Acute Stroke Collaboration (BASC).

INTRODUCTION: Conflicting results from multiple randomised trials indicate that the methods and effects of blood pressure (BP) reduction after acute intracerebral haemorrhage (ICH) are complex. The Blood pressure in Acute Stroke Collaboration is an international collaboration, which aims to determine the optimal management of BP after acute stroke including ICH. METHODS AND ANALYSIS: A systematic review will be undertaken according to the Preferred Reporting Items for Systematic review and Meta-Analysis of Individual Participant Data (IPD) guideline. A search of Cochrane Central Register of Controlled Trials, EMBASE and MEDLINE from inception will be conducted to identify randomised controlled trials of BP management in adults with acute spontaneous (non-traumatic) ICH enrolled within the first 7 days of symptom onset. Authors of studies that meet the inclusion criteria will be invited to share their IPD. The primary outcome will be functional outcome according to the modified Rankin Scale. Safety outcomes will be early neurological deterioration, symptomatic hypotension and serious adverse events. Secondary outcomes will include death and neuroradiological and haemodynamic variables. Meta-analyses of pooled IPD using the intention-to-treat dataset of included trials, including subgroup analyses to assess modification of the effects of BP lowering by time to treatment, treatment strategy and patient's demographic, clinical and prestroke neuroradiological characteristics. ETHICS AND DISSEMINATION: No new patient data will be collected nor is there any deviation from the original purposes of each study where ethical approvals were granted; therefore, further ethical approval is not required. Results will be reported in international peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42019141136.

Management of moderate and severe traumatic brain injury.

Traumatic brain injury (TBI) is a common disorder with high morbidity and mortality, accounting for one in every three deaths due to injury. Older adults are especially vulnerable. They have the highest rates of TBI-related hospitalization and death. There are about 2.5 to 6.5 million US citizens living with TBI-related disabilities. The cost of care is very high. Aside from prevention, little can be done for the initial primary injury of neurotrauma. The tissue damage incurred directly from the inciting event, for example, a blow to the head or bullet penetration, is largely complete by the time medical care can be instituted. However, this event will give rise to secondary injury, which consists of a cascade of changes on a cellular and molecular level, including cellular swelling, loss of membrane gradients, influx of immune and inflammatory mediators, excitotoxic transmitter release, and changes in calcium dynamics. Clinicians can intercede with interventions to improve outcome in the mitigating secondary injury. The fundamental concepts in critical care management of moderate and severe TBI focus on alleviating intracranial pressure and avoiding hypotension and hypoxia. In addition to these important considerations, mechanical ventilation, appropriate transfusion of blood products, management of paroxysmal sympathetic hyperactivity, using nutrition as a therapy, and, of course, venous thromboembolism and seizure prevention are all essential in the management of moderate to severe TBI patients. These concepts will be reviewed using the recent 2016 Brain Trauma Foundation Guidelines to discuss best practices and identify future research priorities.

Preserve encephalus in surgery of trauma: online survey. (P.E.S.T.O).

BACKGROUND: Traumatic brain injury (TBI) is a global health problem. Extracranial hemorrhagic lesions needing emergency surgery adversely affect the outcome of TBI. We conducted an international survey regarding the acute phase management practices in TBI polytrauma patients. METHODS: A questionnaire was available on the World Society of Emergency Surgery website between December 2017 and February 2018. The main endpoints were the evaluation of (1) intracranial pressure (ICP) monitoring during extracranial emergency surgery (EES), (2) hemodynamic management without ICP monitoring during EES, (3) coagulation management, and (4) utilization of simultaneous multisystem surgery (SMS). RESULTS: The respondents were 122 representing 105 trauma centers worldwide. ICP monitoring was utilized in 10-30% of patients at risk of intracranial hypertension (IH) undergoing EES from about a third of the respondents [n = 35 (29%)]. The respondents reported that the safest values of systolic blood pressure during EES in patients at risk of IH were 90-100 mmHg [n = 35 (29%)] and 100-110 mmHg [n = 35 (29%)]. The safest values of mean arterial pressure during EES in patients at risk of IH were > 70 mmHg [n = 44 (36%)] and > 80 mmHg [n = 32 (26%)]. Regarding ICP placement, a large percentage of respondents considered a platelet (PLT) count > 50,000/mm3 [n = 57 (47%)] and a prothrombin time (PT)/activated partial thromboplastin time (aPTT) < 1.5 times the normal control [n = 73 (60%)] to be the safest parameters. For craniotomy, the majority of respondents considered PLT count > 100,000/mm3 [n = 67 (55%)] and a PT/aPTT < 1.5 times the normal control [n = 76 (62%)] to be the safest parameters. Almost half of the respondents [n = 53 (43%)], reported that they transfused red blood cells (RBCs)/plasma (P)/PLTs at a ratio of 1/1/1 in TBI polytrauma patients. SMS was performed in 5-19% of patients, requiring both an emergency neurosurgical operation and EES, by almost half of the respondents [n = 49 (40%)]. CONCLUSIONS: A great variability in practices during the acute phase management of polytrauma patients with severe TBI was identified. These findings may be helpful for future investigations and educational purposes.