Targeted temperature control following traumatic brain injury: ESICM/NACCS best practice consensus recommendations.

AIMS AND SCOPE: The aim of this panel was to develop consensus recommendations on targeted temperature control (TTC) in patients with severe traumatic brain injury (TBI) and in patients with moderate TBI who deteriorate and require admission to the intensive care unit for intracranial pressure (ICP) management. METHODS: A group of 18 international neuro-intensive care experts in the acute management of TBI participated in a modified Delphi process. An online anonymised survey based on a systematic literature review was completed ahead of the meeting, before the group convened to explore the level of consensus on TTC following TBI. Outputs from the meeting were combined into a further anonymous online survey round to finalise recommendations. Thresholds of ≥ 16 out of 18 panel members in agreement (≥ 88%) for strong consensus and ≥ 14 out of 18 (≥ 78%) for moderate consensus were prospectively set for all statements. RESULTS: Strong consensus was reached on TTC being essential for high-quality TBI care. It was recommended that temperature should be monitored continuously, and that fever should be promptly identified and managed in patients perceived to be at risk of secondary brain injury. Controlled normothermia (36.0-37.5 °C) was strongly recommended as a therapeutic option to be considered in tier 1 and 2 of the Seattle International Severe Traumatic Brain Injury Consensus Conference ICP management protocol. Temperature control targets should be individualised based on the perceived risk of secondary brain injury and fever aetiology. CONCLUSIONS: Based on a modified Delphi expert consensus process, this report aims to inform on best practices for TTC delivery for patients following TBI, and to highlight areas of need for further research to improve clinical guidelines in this setting.

Neural Correlates of Pain-Autonomic Coupling in Patients With Complex Regional Pain Syndrome Treated by Repetitive Transcranial Magnetic Stimulation of the Motor Cortex.

OBJECTIVES: Complex regional pain syndrome (CRPS) is a chronic pain condition involving autonomic dysregulation. In this study, we report the results of an ancillary study to a larger clinical trial investigating the treatment of CRPS by neuromodulation. This ancillary study, based on functional magnetic resonance imaging (fMRI), evaluated the neural correlates of pain in patients with CRPS in relation to the sympathetic nervous system and for its potential relief after repetitive transcranial magnetic stimulation of the motor cortex. MATERIALS AND METHODS: Eleven patients with CRPS at one limb (six women, five men, aged 52.0 ± 9.6 years) were assessed before and one month after the end of a five-month repetitive transcranial magnetic stimulation (rTMS) therapy targeting the motor cortex contralateral to the painful limb, by means of electrochemical skin conductance (ESC) measurement, daily pain intensity scores on a visual numerical scale (VNS), and fMRI with motor tasks (alternation of finger movements and rest). The fMRI scans were analyzed voxelwise using ESC and VNS pain score as regressors to derive their neural correlates. The criterion of response to rTMS therapy was defined as ≥30% reduction in VNS pain score one month after treatment compared with baseline. RESULTS: At baseline, ESC values were reduced in the affected limb vs the nonaffected limb. There was a covariance of VNS with brain activation in a small region of the primary somatosensory cortex (S1) contralateral to the painful side on fMRI investigation. After rTMS therapy on motor cortex related to the painful limb, the VNS pain scores significantly decreased by 22% on average. The criterion of response was met in six of 11 patients (55%). In these responders, at one month after treatment, ESC value increased and returned to normal in the CRPS-affected limb, and overall, the increase in ESC correlated with the decrease in VNS after motor cortex rTMS therapy. At one month after treatment, there also was a covariance of both variables (ESC and VNS) with fMRI activation of the S1 region previously mentioned. The fMRI activation of other brain regions (middle frontal gyrus and temporo-parietal junction) showed correlation with ESC values before and after treatment. Finally, we found a positive correlation at one month after treatment (not at baseline) between VNS pain score and fMRI activation in the temporo-parietal junction contralateral to painful side. CONCLUSIONS: This study first shows a functional pain-autonomic coupling in patients with CRPS, which could involve a specific S1 region. However, the modulation of sympathetic sudomotor activities expressed by ESC changes was rather correlated with functional changes in other brain regions. Finally, the pain relief observed at one month after rTMS treatment was associated with a reduced activation of the temporo-parietal junction on the side in which rTMS was performed. These findings open perspectives to define new targets or biomarkers for using rTMS to treat CRPS-associated pain. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02817880.

Management of Cerebral Venous Thrombosis Due to Adenoviral COVID-19 Vaccination.

OBJECTIVE: Cerebral venous thrombosis (CVT) caused by vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of adenovirus-based severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines. In March 2021, after autoimmune pathogenesis of VITT was discovered, treatment recommendations were developed. These comprised immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusion. The aim of this study was to evaluate adherence to these recommendations and its association with mortality. METHODS: We used data from an international prospective registry of patients with CVT after the adenovirus-based SARS-CoV-2 vaccination. We analyzed possible, probable, or definite VITT-CVT cases included until January 18, 2022. Immunomodulation entailed administration of intravenous immunoglobulins and/or plasmapheresis. RESULTS: Ninety-nine patients with VITT-CVT from 71 hospitals in 17 countries were analyzed. Five of 38 (13%), 11 of 24 (46%), and 28 of 37 (76%) of the patients diagnosed in March, April, and from May onward, respectively, were treated in-line with VITT recommendations (p < 0.001). Overall, treatment according to recommendations had no statistically significant influence on mortality (14/44 [32%] vs 29/55 [52%], adjusted odds ratio [OR] = 0.43, 95% confidence interval [CI] = 0.16-1.19). However, patients who received immunomodulation had lower mortality (19/65 [29%] vs 24/34 [70%], adjusted OR = 0.19, 95% CI = 0.06-0.58). Treatment with non-heparin anticoagulants instead of heparins was not associated with lower mortality (17/51 [33%] vs 13/35 [37%], adjusted OR = 0.70, 95% CI = 0.24-2.04). Mortality was also not significantly influenced by platelet transfusion (17/27 [63%] vs 26/72 [36%], adjusted OR = 2.19, 95% CI = 0.74-6.54). CONCLUSIONS: In patients with VITT-CVT, adherence to VITT treatment recommendations improved over time. Immunomodulation seems crucial for reducing mortality of VITT-CVT. ANN NEUROL 2022;92:562-573.

Decompressive surgery in cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia.

BACKGROUND AND PURPOSE: Cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) is an adverse drug reaction occurring after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. CVST-VITT patients often present with large intracerebral haemorrhages and a high proportion undergoes decompressive surgery. Clinical characteristics, therapeutic management and outcomes of CVST-VITT patients who underwent decompressive surgery are described and predictors of in-hospital mortality in these patients are explored. METHODS: Data from an ongoing international registry of patients who developed CVST within 28 days of SARS-CoV-2 vaccination, reported between 29 March 2021 and 10 May 2022, were used. Definite, probable and possible VITT cases, as defined by Pavord et al. (N Engl J Med 2021; 385: 1680-1689), were included. RESULTS: Decompressive surgery was performed in 34/128 (27%) patients with CVST-VITT. In-hospital mortality was 22/34 (65%) in the surgical and 27/94 (29%) in the non-surgical group (p < 0.001). In all surgical cases, the cause of death was brain herniation. The highest mortality rates were found amongst patients with preoperative coma (17/18, 94% vs. 4/14, 29% in the non-comatose; p < 0.001) and bilaterally absent pupillary reflexes (7/7, 100% vs. 6/9, 67% with unilaterally reactive pupil, and 4/11, 36% with bilaterally reactive pupils; p = 0.023). Postoperative imaging revealed worsening of index haemorrhagic lesion in 19 (70%) patients and new haemorrhagic lesions in 16 (59%) patients. At a median follow-up of 6 months, 8/10 of surgical CVST-VITT who survived admission were functionally independent. CONCLUSIONS: Almost two-thirds of surgical CVST-VITT patients died during hospital admission. Preoperative coma and bilateral absence of pupillary responses were associated with higher mortality rates. Survivors often achieved functional independence.

Efficacy and Safety of Early Administration of 4-Factor Prothrombin Complex Concentrate in Patients With Trauma at Risk of Massive Transfusion: The PROCOAG Randomized Clinical Trial.

Importance: Optimal transfusion strategies in traumatic hemorrhage are unknown. Reports suggest a beneficial effect of 4-factor prothrombin complex concentrate (4F-PCC) on blood product consumption. Objective: To investigate the efficacy and safety of 4F-PCC administration in patients at risk of massive transfusion. Design, Setting, and Participants: Double-blind, randomized, placebo-controlled superiority trial in 12 French designated level I trauma centers from December 29, 2017, to August 31, 2021, involving consecutive patients with trauma at risk of massive transfusion. Follow-up was completed on August 31, 2021. Interventions: Intravenous administration of 1 mL/kg of 4F-PCC (25 IU of factor IX/kg) vs 1 mL/kg of saline solution (placebo). Patients, investigators, and data analysts were blinded to treatment assignment. All patients received early ratio-based transfusion (packed red blood cells:fresh frozen plasma ratio of 1:1 to 2:1) and were treated according to European traumatic hemorrhage guidelines. Main Outcomes and Measures: The primary outcome was 24-hour all blood product consumption (efficacy); arterial or venous thromboembolic events were a secondary outcome (safety). Results: Of 4313 patients with the highest trauma level activation, 350 were eligible for emergency inclusion, 327 were randomized, and 324 were analyzed (164 in the 4F-PCC group and 160 in the placebo group). The median (IQR) age of participants was 39 (27-56) years, Injury Severity Score was 36 (26-50 [major trauma]), and admission blood lactate level was 4.6 (2.8-7.4) mmol/L; prehospital arterial systolic blood pressure was less than 90 mm Hg in 179 of 324 patients (59%), 233 patients (73%) were men, and 226 (69%) required expedient hemorrhage control. There was no statistically or clinically significant between-group difference in median (IQR) total 24-hour blood product consumption (12 [5-19] U in the 4F-PCC group vs 11 [6-19] U in the placebo group; absolute difference, 0.2 U [95% CI, -2.99 to 3.33]; P = .72). In the 4F-PCC group, 56 patients (35%) presented with at least 1 thromboembolic event vs 37 patients (24%) in the placebo group (absolute difference, 11% [95% CI, 1%-21%]; relative risk, 1.48 [95% CI, 1.04-2.10]; P = .03). Conclusions and Relevance: Among patients with trauma at risk of massive transfusion, there was no significant reduction of 24-hour blood product consumption after administration of 4F-PCC, but thromboembolic events were more common. These findings do not support systematic use of 4F-PCC in patients at risk of massive transfusion. Trial Registration: ClinicalTrials.gov Identifier: NCT03218722.

Cerebral vasospasm in children with subarachnoid hemorrhage: frequency, diagnosis, and therapeutic management.

BACKGROUND: The present study explores the frequency, diagnostic approach, and therapeutic management of cerebral vasospasm in a cohort of children with moderate-to-severe traumatic and nontraumatic subarachnoid hemorrhage (SAH). METHODS: This was a single-center retrospective study performed over a 10-year period, from January 2010 to December 2019. Children aged from one month to 18 years who were admitted to the pediatric or adult intensive care unit with a diagnosis of SAH were eligible. Cerebral vasospasm could be suspected by clinical signs or transcranial Doppler (TCD) criteria (mean blood flow velocity > 120 cm/s or an increase in mean blood flow velocity by > 50 cm/s within 24 h) and then confirmed on cerebral imaging (with a reduction to less than 50% of the caliber of the cerebral artery). RESULTS: Eighty patients aged 8.6 years (3.3-14.8 years, 25-75th centiles) were admitted with an initial Glasgow Coma Scale score of 8 (4-12). SAH was nontraumatic in 21 (26%) patients. A total of 14/80 patients (18%) developed cerebral vasospasm on brain imaging on day 6 (5-10) after admission, with a predominance of nontraumatic SAH (12/14). The diagnosis of cerebral vasospasm was suspected on clinical signs and/or significant temporal changes in TCD monitoring (7 patients) and then confirmed on cerebral imaging. Thirteen of 14 patients with vasospasm were successfully treated using a continuous intravenous infusion of milrinone. The Pediatric Cerebral Performance Category score at discharge from the intensive care unit was comparable between children with vasospasm (score of 2 [1-4]) vs. children without vasospasm (score of 4 [2-4]) (p = 0.09). CONCLUSIONS: These findings indicate that cerebral vasospasm exists in pediatrics, particularly after nontraumatic SAH. The use of TCD and milrinone may help in the diagnostic and therapeutic management of cerebral vasospasm.

Using Nonheparin Anticoagulant to Treat a Near-Fatal Case With Multiple Venous Thrombotic Lesions During ChAdOx1 nCoV-19 Vaccination-Related Vaccine-Induced Immune Thrombotic Thrombocytopenia.

OBJECTIVES: To describe the successful recovery from multiple and life-threatening venous thrombosis after ChAdOx1 nCoV-19 vaccination. DESIGN: Case report. SETTING: University Hospital. PATIENT: Few days after the first dose of the ChAdOx1 nCoV-19 vaccine, a 21-year-old woman experienced massive thrombosis in the deep and superficial cerebral veins together with seizures, neurologic focal deficit, and thrombocytopenia. In the neurointensive care unit, her condition worsened despite early decompressive craniectomy. She developed bilateral segmental pulmonary embolism, left hepatic, and left external iliac venous thrombosis. INTERVENTION: Argatroban (0.5-2.2 µg/kg/min) and high-dose IV immunoglobulin (1 g/kg/d for 2 consecutive days) were initiated on day 6 after admission. With these therapies, there was a gradual resolution of multiple sites of venous thrombosis, and platelet count returned to normal. The patient left the ICU with full consciousness, expressive aphasia, and right hemiparesis. CONCLUSIONS: This case of vaccine-induced immune thrombotic thrombocytopenia shows that a good outcome can be obtained even with multiple and life-threatening venous thrombotic lesions. Argatroban and high-dose IV immunoglobulin along with management of severe cerebral venous thrombosis played a major role in this epilogue.

Hypertonic Sodium Lactate to Alleviate Functional Deficits Following Diffuse Traumatic Brain Injury: An Osmotic or a Lactate-Related Effect?

BACKGROUND: There has been growing interest in the use of hypertonic sodium lactate (HSL) solution following traumatic brain injury (TBI) in humans. However, little is known about the effects of HSL on functional deficits with respect to the hyperosmotic nature of HSL. METHODS: We have compared the effects of HSL solution and isotonic saline solution using sensorimotor and cognitive tests for 14 days post-trauma in animals. Thirty minutes after trauma (impact-acceleration model), anesthetized rats were randomly allocated to receive a 2-h infusion of isotonic saline solution (TBI-saline group) or HSL (TBI-HSL group) (n = 10 rats per group). In another series of experiments using a similar protocol, the effects of equiosmolar doses of HSL and hypertonic saline solution (HSS) were compared in TBI rats (n = 10 rats per group). Blood lactate and ion concentrations were measured during the 2-h infusions. RESULTS: Compared to the TBI-saline group, the TBI-HSL group had a reduced latency to complete the adhesive removal test: 6 s (5-9) (median [25-75th centiles]) versus 13 s (8-17) on day 7, and 5 s (5-9) versus 11 s (8-26) on day 14 (P < 0.05), respectively, and a shorter delay to complete the radial arm maze test on day 7: 99 s (73-134) versus 176 s (127-300), respectively (P < 0.05). However, no differences were found between the TBI-HSL and TBI-HSS groups in neurocognitive tests performance. Compared to the TBI-saline group, the HSL and HSS groups had higher serum osmolality: 318 mOsm/Kg (315-321) and 315 mOsm/Kg (313-316) versus 307 mOsm/Kg (305-309), respectively (P < 0.05), and the HSL group had a higher serum lactate concentration: 6.4 mmol/L (5.3-7.2) versus 1.5 mmol/L (1.1-1.9) and 1.6 mmol/L (1.5-1.7), respectively (P < 0.05). CONCLUSIONS: These results indicate that improvements in cognitive and sensorimotor tests with HSL infusion post-TBI could be related to elevation of serum osmolality, not to exogenous administration of lactate.

Impact of Head-of-Bed Posture on Brain Oxygenation in Patients with Acute Brain Injury: A Prospective Cohort Study.

BACKGROUND: Therapeutic head positioning plays a role in the management of patients with acute brain injury. Although intracranial pressure (ICP) is typically lower in an upright posture than in a flat position, limited data exist concerning the effect of upright positioning on brain oxygenation and circulation. We sought to determine the impact of supine (0°) and semirecumbent (15° and 30°) postures on ICP, brain oxygenation, and brain circulation. METHODS: An observational cohort study was conducted between February 2012 and September 2015. Twenty-three patients with severe acute brain injury were successively observed at head elevations of 30°, 15°, and 0°. Postural-induced changes in ICP, cerebral perfusion pressure, brain tissue oxygenation pressure, and transcranial Doppler findings were simultaneously measured during three repeated experiments: 24 h after admission to the intensive care unit (exp1), 24 h later (exp2), and 96 h later (exp3). Cerebral perfusion pressure, arterial blood gases, hemoglobin content, and body temperature remained unchanged during the three experiments. RESULTS: Using linear random-slope mixed models, we found that during the early phase of acute brain injury (exp1), lowering the head posture from 30° to 15°, and then to 0°, was associated with a gradual mean ICP increase of 2.6 mm Hg (1.4-3.7 mm Hg; P < 0.001); and from 30° to 0°, an increase of 7.4 mm Hg (6.3-8.6 mm Hg; P < 0.001). Furthermore, brain tissue oxygenation pressure and mean blood flow velocity improved when the head posture was lowered from 30° to 0° by 1.2 mm Hg (0.2-2.3 mm Hg) and 4.1 cm/s (0.0-8.2 cm/s), respectively (both P < 0.05). CONCLUSIONS: Changing the positioning of stable patients with acute brain injury resulted in opposite changes of ICP versus brain oxygenation and circulation. This information supports the concept of an individualized approach to head positioning that is based on the multimodal monitoring of brain parameters.

Oxygen desaturation and time burden during tracheobronchial endoscopy for suspected foreign body in toddlers.

Tracheobronchial endoscopy with general anaesthesia for suspected foreign body aspiration exposes toddlers to acute hypoxemia. Better quantification of intraoperative hypoxemia could help identify and manage the most severe patients. We explored the hypoxic burden approach to account for both duration and depth of desaturation episodes during the procedure and determined risk factors for high hypoxic burden. We retrospectively analysed tracheobronchial endoscopies performed from September 2015 to September 2018 in children ≤ 36 months for suspected foreign body aspiration, in two French university hospitals. The hypoxic burden (area under 90% of the SpO2/time curve) was calculated. The median of non-zero burdens was used to delineate a subgroup with high hypoxic burden. Risk factors for high hypoxic burden were identified using multivariable analysis. Of 96 procedures, 56 (58%) were associated with at least one SpO2 value < 90%. Of them, the median [interquartile] hypoxic burden was 25 [5-87] %.min. Bradycardia < 100 bpm occurred in 11 procedures (11%). Initial admission to general hospitals (OR 0.23, 95% CI 0.06-0.86) and airway anaesthesia with topical lidocaine (OR 0.15, 95% CI 0.03-0.62) were associated with a reduced risk of high hypoxic burden. High hypoxic burden was associated with an increased risk of postoperative invasive ventilation (OR 32, 95% CI 1.7-617) and of hospital stay > 24 h (OR 4.0, 95% CI 1.6-10). No postoperative neurological sequelae were found. The hypoxic burden approach, when applied in tracheobronchial endoscopy for suspected foreign body aspiration in toddlers, enabled the quantification of hypoxemia and the search for specific risk factors.

Preoperative Screening for Obstructive Sleep Apnea Using Alternative Scoring Models of the Sleep Tiredness Observed Pressure-Body Mass Index Age Neck Circumference Gender Questionnaire: An External Validation.

BACKGROUND: The Sleep Tiredness Observed Pressure-Body mass index Age Neck circumference Gender (STOP-Bang) questionnaire is a validated preoperative screening tool for identifying patients with obstructive sleep apnea (OSA). Although it has a high sensitivity at scores ≥3, its specificity is moderate, particularly for scores of 3-4. This study aimed to externally validate the STOP-Bang questionnaire and the alternative scoring models that have been proposed to improve its predictive performance. METHODS: This prospective cohort study included 115 surgical patients with preoperative STOP-Bang scores of 3-8. Type 3 sleep recordings identified moderate-to-severe OSA, reflected by an apnea-hypopnea index (AHI) of >15. Patients were categorized into 2 subgroups: patients with an intermediate (STOP-Bang 3-4) or a high risk of OSA (STOP-Bang 5-8). For patients with scores of 3-4, we tested approaches identified in previous studies: stepwise stratification of the STOP-Bang questionnaire and additional preoperative measurement of serum bicarbonate concentrations. RESULTS: The incidence of moderate-to-severe OSA was significantly higher in patients with STOP-Bang scores of 5-8 than in patients with scores of 3-4: 45 of 58 patients (78%) versus 30 of 57 patients (53%), respectively (P < .01). For patients with STOP-Bang scores of 3-4, we found no differences regarding their OSA diagnosis between patients included in the alternative scoring models and those not included. CONCLUSIONS: The STOP-Bang questionnaire detected moderate-to-severe OSA patients when scores reached 5-8. However, its performance was altered in patients with STOP-Bang scores of 3-4, and alternative scoring models with specific combinations of factors failed to improve the screening of these patients.

Evidence for Mannitol as an Effective Agent Against Intracranial Hypertension: An Individual Patient Data Meta-analysis.

Mannitol is currently used to reduce intracranial pressure (ICP), but the evidence supporting its usefulness has been questioned. We aim to meta-analyze the effectiveness of mannitol in reducing ICP in adult patients with cerebral injuries and its dependency on baseline ICP values, comparing findings from individual patient data (IPD) and aggregated data (AD) meta-analysis performed on the same studies. We searched the Medline database, with no time limitation, through March 1, 2019. We selected studies for which IPD were available, with a before-after design, concerning adult patients with traumatic cerebral hemorrhages, subarachnoid hemorrhages, or hemorrhagic and ischemic stroke, treated with mannitol for increased intracranial hypertension. We extracted ICP values at baseline and at different time-points, and mannitol doses. We used a multilevel approach to account for multiple measurements on the same patient and for center variability. The AD meta-analysis and meta-regression were conducted using random-effects models. Three studies published IPD, and four authors shared their datasets. Two authors did not own their datasets anymore. Eight authors were unreachable, while 14 did not answer to our request. Overall, 7 studies provided IPD for 98 patients. The linear mixed-effects model showed that ICP decreased significantly after mannitol administration from an average baseline value of 22.1 mmHg to 16.8, 12.8, and 9.7 mmHg at 60, 120, and 180 min after mannitol administration. ICP reduction was proportional to baseline values with a 0.64 mmHg decrease for each unitary increment of the initial ICP value. Dose did not influence ICP reduction. The AD meta-analysis, based on data collected between 30 and 60 min from mannitol administration not accounting for multiple time-point measurements, overestimated ICP reduction (10 mmHg), while meta-regression provided similar results (0.66 mmHg decrease for each unitary increase of initial ICP). Mannitol is effective in reducing pathological ICP, proportionally to the degree of intracranial hypertension. IPD meta-analysis provided a more precise quantification of ICP variation than the AD approach.

Using Pupillary Pain Index to Assess Nociception in Sedated Critically Ill Patients.

BACKGROUND: Pupillary reflex dilation is a reliable indicator of response to noxious stimulation. In a proof of concept study, we investigated the performance of pupillary pain index, a new score derived from pupillary reflex dilation measurements, to predict nociceptive response to endotracheal suctioning in sedated critically ill patients. METHODS: Twenty brain-injured and 20 non-brain-injured patients were studied within 48 hours of admission (T1) in the intensive care unit and at 48-72 hours later (T2). Video-based pupillometer was used to determine pupillary reflex dilation during tetanic stimulation. The tetanic stimulation (100 Hz) was applied to the skin area innervated by the ulnar nerve and was stepwise increased from 10 to 60 mA until pupil size had increased by 13% compared to baseline. The maximum intensity value allowed the determination of a pupillary pain index score ranging from 1 (no nociception) to 9 (high nociception). The Behavioral Pain Scale response to endotracheal suctioning was measured thereafter. RESULTS: Behavioral Pain Scale responses to endotracheal suctioning and pupillary pain index scores were positively correlated at T1 and T2 (both P < .01). After adjustments for repeated measurements and group of patients, the area under the receiver operating characteristic curve of pupillary pain index to predict Behavioral Pain Scale response to endotracheal suctioning was of 0.862 (95% CI, 0.714-0.954). In the combined set of patients, a pupillary pain index score of ≤4 could predict no nociceptive response to endotracheal suctioning with a sensitivity of 88% (95% CI, 68%-97%) and a specificity of 79% (95% CI, 66%-88%). By contrast with endotracheal suctioning, tetanic stimulation had no effect on intracranial pressure in the brain-injured group. CONCLUSIONS: These results are a proof of concept. The nociceptive response to endotracheal suctioning could be accurately predicted using the determination of pupillary pain index score in sedated critically ill patients whether they have brain injury or not.

Preoperative Statin Treatment Is Not Associated with Reduced Postoperative Mortality or Morbidity in Patients Undergoing Isolated Valve Surgery.

INTRODUCTION: Previous studies have shown that statin use before coronary surgery decreases the mortality and morbidity. This benefit was not clearly detected in isolated valve surgery. The aim of this study was to assess the effect of preoperative statin therapy on postoperative complications and mortality in a large group of patients undergoing valve surgery. PATIENTS, MATERIALS, AND METHODS: The data of consecutive patients undergoing isolated valve replacement during an 8-year period were retrospectively reviewed from a prospective database. Mortality was compared between the patients who received preoperative statin (statin group [SG]) and those who did not receive statin (control group [CG]) after adjustment on EuroSCORE. Main postoperative complications and mortality were compared between the 2 groups by using a propensity score analysis. RESULTS: During the study period, 1115 patients were prospectively included, 796 in the CG group and 319 in the SG. The SG patients were significantly older, had more cardiovascular risk factors (hypertension, diabetes, and weight) than the CG patients, and benefited from more elective surgery or aortic valve replacement. No difference in mortality was found between the groups: 4.4% in the SG and 4.5% in the CG, P = .95. Multivariate analysis also revealed no effect of statin on mortality, according to the type of surgery (aortic valve surgery alone or any kind of valve surgery) (P = .93), or the elective or urgent nature of the surgery (P = .67). Statin did not predict mortality after stratification with the EuroSCORE or the Parsonnet score. No difference was found between the 2 groups for postoperative complications (24-hour bleeding, atrial fibrillation, renal failure, length of mechanical ventilation, or hospital stay) and mortality after adjustment with a propensity score. DISCUSSION: This study found no difference in mortality or morbidity associated with preoperative statin therapy after isolated valve surgery.

Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU.

OBJECTIVE: To update and expand the 2013 Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the ICU. DESIGN: Thirty-two international experts, four methodologists, and four critical illness survivors met virtually at least monthly. All section groups gathered face-to-face at annual Society of Critical Care Medicine congresses; virtual connections included those unable to attend. A formal conflict of interest policy was developed a priori and enforced throughout the process. Teleconferences and electronic discussions among subgroups and whole panel were part of the guidelines' development. A general content review was completed face-to-face by all panel members in January 2017. METHODS: Content experts, methodologists, and ICU survivors were represented in each of the five sections of the guidelines: Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption). Each section created Population, Intervention, Comparison, and Outcome, and nonactionable, descriptive questions based on perceived clinical relevance. The guideline group then voted their ranking, and patients prioritized their importance. For each Population, Intervention, Comparison, and Outcome question, sections searched the best available evidence, determined its quality, and formulated recommendations as "strong," "conditional," or "good" practice statements based on Grading of Recommendations Assessment, Development and Evaluation principles. In addition, evidence gaps and clinical caveats were explicitly identified. RESULTS: The Pain, Agitation/Sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) panel issued 37 recommendations (three strong and 34 conditional), two good practice statements, and 32 ungraded, nonactionable statements. Three questions from the patient-centered prioritized question list remained without recommendation. CONCLUSIONS: We found substantial agreement among a large, interdisciplinary cohort of international experts regarding evidence supporting recommendations, and the remaining literature gaps in the assessment, prevention, and treatment of Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) in critically ill adults. Highlighting this evidence and the research needs will improve Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) management and provide the foundation for improved outcomes and science in this vulnerable population.

Hepatitis E Virus Infection after Platelet Transfusion in an Immunocompetent Trauma Patient.

Hepatitis E virus (HEV) infection causes acute liver disease, but severe infections are rare in immunocompetent patients. We describe a case of HEV infection in a previously healthy male trauma patient in France who received massive transfusions. Genotyping confirmed HEV in a transfused platelet pool and the donor.

Clinical Judgment Is Not Reliable for Reducing Whole-body Computed Tomography Scanning after Isolated High-energy Blunt Trauma.

BACKGROUND: The purpose of this study was to test the diagnostic performance of clinical judgment for the prediction of a significant injury with whole-body computed tomography scanning after high-energy trauma. METHODS: The authors conducted an observational prospective study in a single level-I trauma center. Adult patients were included if they had an isolated high-energy injury. Senior trauma leaders were asked to make a clinical judgment regarding the likelihood of a significant injury before performance of a whole-body computed tomography scan. Clinical judgments were recorded using a probability diagnosis scale. The primary endpoint was the diagnosis of a serious-to-critical lesion on the whole-body computed tomography scan. Diagnostic performance was assessed using receiver operating characteristic analysis. RESULTS: Of the 354 included patients, 127 patients (36%) had at least one injury classified as abbreviated injury score greater than or equal to 3. The area under the receiver operating characteristic curve of the clinical judgment to predict a serious-to-critical lesion was 0.70 (95% CI, 0.64 to 0.75%). The sensitivity of the clinical judgment was 82% (95% CI, 74 to 88%), and the specificity was 49% (95% CI, 42 to 55%). No patient with a strict negative clinical examination had a severe lesion (n = 19 patients). The sensitivity of the clinical examination was 100% (95% CI, 97 to 100%) and its specificity was 8% (95% CI, 5 to 13%). CONCLUSIONS: Clinical judgment alone is not sufficient to reduce whole-body computed tomography scan use. In patients with a strictly normal physical examination, whole-body computed tomography scanning might be avoided, but this result deserves additional study in larger and more diverse populations of trauma patients.

Does continuous wound infiltration enhance baseline intravenous multimodal analgesia after posterior spinal fusion surgery? A randomized, double-blinded, placebo-controlled study.

PURPOSE: There has been a growing interest in continuous local anaesthetic wound infiltration as a non-opioid technique for postoperative pain relief. The impact of this modality on baseline analgesia after spinal fusion surgery has however been inconclusive. We tested whether continuous wound infiltration with ropivacaine can enhance postoperative analgesia compared to a baseline intravenous multimodal analgesia protocol after spinal fusion surgery. METHODS: In this randomized, double-blinded, placebo-controlled study, a multiholed 19-gauge catheter was placed at the end of the surgical procedure through the wound to permit the continuous administration (8 ml/h) of ropivacaine 0.2 % (ropivacaine group; n = 19 patients) or saline (control group; n = 20 patients) during the first 48 postoperative hours (H48). Both groups received intraoperative low-dose ketamine, a combination of acetaminophen, non-steroidal anti-inflammatory drug, and nefopam over the same postoperative period, and morphine delivered by a patient-controlled analgesia (PCA) device. RESULTS: Morphine consumption was comparable between the two groups both at H48, 38 mg (26:52) (median, 25th:75th percentile) (control group) versus 43 mg (19:74) (ropivacaine group), and at H24, 18 mg (16:22) versus 22 mg (9:35) respectively. Pain scores at rest and during mobilization, quality of postoperative sleep, and morphine-related side effects were comparable between the two groups at H24 and H48. CONCLUSION: Our findings indicate that no additional analgesia was provided with continuous wound infiltration of ropivacaine compared to a baseline intravenous multimodal analgesia protocol after spinal fusion surgery. TRIAL REGISTRATION: Clinicaltrials.gov #NCT01743794.

Using external lumbar CSF drainage to treat communicating external hydrocephalus in adult patients after acute traumatic or non-traumatic brain injury.

BACKGROUND: Despite various treatments to control intracranial pressure (ICP) after brain injury, patients may present a late onset of high ICP or a poor response to medications. External lumbar drainage (ELD) can be considered a therapeutic option if high ICP is due to communicating external hydrocephalus. We aimed at describing the efficacy and safety of ELD used in a cohort of traumatic or non-traumatic brain-injured patients. METHODS: In this multicentre retrospective analysis, patients had a delayed onset of high ICP after the initial injury and/or a poor response to ICP treatments. ELD was considered in the presence of radiological signs of communicating external hydrocephalus. Changes in ICP values and side effects following the ELD procedure were reported. RESULTS: Thirty-three patients with a median age of 51 years (25-75th percentile: 34-61 years) were admitted after traumatic (n = 22) or non-traumatic (n = 11) brain injuries. Their initial Glasgow Coma Scale score was 8 (4-11). Eight patients underwent external ventricular drainage prior to ELD. Median time to ELD insertion was 5 days (4-8) after brain insult. In all patients, ELD was dramatically effective in lowering ICP: 25 mmHg (20-31) before versus 7 mmHg (3-10) after (p < 0.001). None of the patients showed adverse effects such as pupil changes or intracranial bleeding after the procedure. One patient developed an ELD-related infection. CONCLUSIONS: These findings indicate that ELD may be considered potentially effective in controlling ICP, remaining safe if a firm diagnosis of communicating external hydrocephalus has been made.