Patient Selection in a Pragmatic Study on the Management of Patients with Brain Arteriovenous Malformations.

BACKGROUND: The Treatment of Brain Arteriovenous Malformations Study (TOBAS) is an all-inclusive pragmatic study comprising 2 randomized clinical trials (RCTs). Patients excluded from the RCTs are followed in parallel treatment and observation registries, allowing a comparison between RCT and registry patients. METHODS: The first randomized clinical trial (RCT-1) offers 1:1 randomized allocation of intervention versus conservative management for patients with arteriovenous malformation (AVM). The second randomized clinical trial (RCT-2) allocates 1:1 pre-embolization or no pre-embolization to surgery or radiosurgery patients judged treatable with or without embolization. Characteristics of RCT patients are reported and compared to registry patients. RESULTS: From June 2014 to May 2021, 1010 patients with AVM were recruited; 498 patients were observed and 373 were included in the treatment registries. Randomized allocation in RCT-1 was applied to 139 (26%) of the 512 patients (including 127 of 222 [57%] with unruptured AVMs) considered for curative treatment. RCT-1 AVM patients differed (in rupture status, Spetzler-Martin grade and baseline modified Rankin Score) from those in the observation or treatment registries (P < 0.001). Most patients had small (<3 cm; 71%) low-grade (Spetzler-Martin I-II; 64%) unruptured (91%) AVMs. The allocated management was conservative (n = 71) or curative (n = 68), using surgery (n = 39), embolization (n = 16), or stereotactic radiosurgery (n = 13). Pre-embolization was considered for 179/309 (58%) patients allocated/assigned to surgery or stereotactic radiosurgery; 87/179 (49%) were included in RCT-2. RCT-2 patient AVMs differed in size, eloquence and grade from patients of the pre-embolization registry (P < 0.01). Most had small (<3 cm in 82%) low-grade (83%) AVMs in non-eloquent brain (64%). CONCLUSIONS: Patients included in the RCTs differ significantly from registry patients. Meaningful results can be obtained if multiple centers actively participate in the TOBAS RCTs.

Endoscopic transsphenoidal surgery for non-functioning pituitary adenoma: Learning curve and surgical results in a prospective series during initial experience.

Background: To report the initial experience of surgery for non-functioning pituitary adenoma (NFPA) from a neurosurgeon in a dedicated residency training endoscopic transsphenoidal (ETS) program, and detail the surgical and clinical outcomes during this period. Methods: A prospective series of all patients operated for NFPA, using an ETS approach, during the three first years of experience of a newly board-certified neurosurgeon was analysed. Clinical, radiological and peri-operative data were collected. Extent of resection (EOR) was determined by formal volumetric analysis. Impact of the learning curve and predictive factors of gross total resection (GTR) were determined. Results: Fifty-three patients with NFPA were included in this prospective cohort which was divided in two periods of time ("First period": 30 first cases, and "second period": 23 following cases). Baseline characteristics of the patients in the two periods were similar. Overall occurrence of complication was 22% and was not significantly different in the two periods of time. No patient had severe neurological complication. Gross total resection was achieved in 70% of patients. Mean Extent of resection was 96%. In a multiple linear regression model, a higher EOR was positively correlated with experience (p = 0.018) and negatively correlated with Knosp Score equal to 4 (p < 0.001). Predictive factors for GTR were Higher Knosp grade (p = 0,01), higher pre-operative volume (p = 0.03), and second period of time (p = 0.01). Conclusion: NFPA surgery can be safe and efficient during the learning period. Dedicated intensive learning, careful patient selection and multidisciplinary work are key to shorten the learning curve and achieve satisfactory results.

Optimal intracranial pressure in patients with aneurysmal subarachnoid hemorrhage treated with coiling and requiring external ventricular drainage.

Optimal management of intracranial pressure (ICP) among aneurysmal subarachnoid hemorrhage (aSAH) patients requiring external ventricular drainage (EVD) is controversial. To analyze predictors of delayed cerebral ischemia (DCI)-related cerebral infarction after aSAH and the influence of ICP values on DCI, we prospectively collected consecutive patients with aSAH receiving coiling and requiring EVD. Predictors of DCI-related cerebral infarction (new CT hypodensities developed within the first 3 weeks not related to other causes) were studied. Vasospasm and brain hypoperfusion were studied with CT angiography and CT perfusion (RAPID-software). Among 50 aSAH patients requiring EVD, 21 (42%) developed DCI-related cerebral infarction, while 27 (54%) presented vasospasm. Mean ICP ranged between 2 and 19 mmHg. On the multivariate analysis, the mean ICP (OR = 2, 95%CI = 1.01-3.9, p = 0.042) and the mean hypoperfusion volume on Tmax delay > 6 (OR = 1.2, 95%CI = 1.01-1.3, p = 0.025) were independent predictors of DCI. To predict DCI-related cerebral infarction, Tmax delay > 6 s presented the highest AUC (0.956, SE = 0.025), with a cutoff value of 18 ml showing sensitivity, specificity, PPV, NPV, and accuracy of 90.5% (95%CI = 69-98.8%), 86.2% (95%CI = 68.4-96%), 82.6% (95%CI = 65.4-92%), 92.5% (95%CI = 77-98%), and 88% (95%CI = 75-95%), respectively. The AUC of the mean ICP was 0.825 (SE = 0.057), and the best cutoff value was 6.7 mmHg providing sensitivity, specificity, PPV, NPV, and accuracy of 71.4% (95%CI = 48-89%), 62% (95%CI = 42-79%), 58% (95%CI = 44-70%), 75% (95%CI = 59-86%), and 66% (95%CI = 51-79%) for the prediction of DCI-related cerebral infarction, respectively. Among aSAH patients receiving coiling and EVD, lower ICP (< 6.7 mmHg in our study) could potentially be beneficial in decreasing DCI-related cerebral infarction. Brain hypoperfusion with a volume > 18 ml at Tmax delay > 6 s presents a high sensibility and specificity in prediction of DCI-related cerebral infarction.

Typology of Published Randomized Controlled Trials Investigating Initial Ventilation Strategy in Critically Ill Patients With Acute Respiratory Failure: A Methodologic Review.

BACKGROUND: Randomized controlled trials (RCTs) in patients with hypoxemic acute respiratory failure (ARF) often failed to show survival benefits and resulted in varying clinical end points. RESEARCH QUESTION: This methodologic review was conducted of published RCTs on ARF, with a careful attention to whether the study results were positive or negative. STUDY DESIGN AND METHODS: MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science were searched for published RCTs in adult patients with ARF between January 1995 and December 2019. The objective was to investigate sources of heterogeneity and factors associated with a positive RCT (ie, with a significant difference on the primary end point). To determine the importance of the primary end point choice, end points were classified as follows: (1) respiratory event end points (corresponding to modification of the ventilation support); (2) physiologic/clinical end points (corresponding to oxygenation or clinical parameters); and (3) mortality. The Cochrane risk-of-bias tool was used to assess study quality. RESULTS: Seventy-four RCTs were included (57% were single-center RCTs) comparing mainly oxygenation/ventilation strategies (95%) in patients with various ARF causes (62%); studies were stopped prematurely in 20% of the trials. A standardized management of ARF was observed in 24 (32%) trials. Twenty-two distinct primary end points have been used, the first of which were those based on respiratory events (44 RCTs [49%]), namely intubation in 76% of the cases. Physiologic/clinical end points have been used in 21 trials (29%) and mortality in nine (12%). Overall, 42 (57%) RCTs were positive, 52% in studies with respiratory event end points, 76% in studies with physiologic/clinical end points, and 33% in studies with mortality end points. Adjusted for study quality (Cochrane risk-of-bias tool), factors associated with a positive RCT included clinically based primary end points (OR, 8.40; 95% CI, 1.35-65.79), the use of standardized ARF management (OR, 4.55; 95% CI, 1.02-22.88), and single-center trials (OR, 3.85; 95% CI, 1.25-13.11). INTERPRETATION: The typology of published RCTs in patients with ARF could be used to frame future trial designs in this field and guide clinicians and researchers toward optimal research transfer to the bedside.

Endoscopic subperichondrial transseptal transsphenoidal approach is safe and efficient for non-extended pituitary surgery.

PURPOSE: To report the results of a series of patients undergoing the endoscopic subperichondrial transseptal (STRAS) approach for pituitary surgery and to evaluate the efficiency and the safety of this approach. METHODS: This is a single-centre retrospective study including all patients undergoing pituitary lesion resection through the STRAS approach from January 2002 to December 2017 by a multidisciplinary surgical team (ENT and neurosurgeon). Demographic data, tumour type, complication rate and pre- and post-operative visual, endocrine and tumour status were retrospectively analysed. RESULTS: 119 patients were included in the study, 80 (67%) presenting macroadenoma, 24 (20%) microadenoma (20%) and 6 (5%) giant adenoma. 61 (51%) patients had secreting adenoma and 51 (42%) patient had non-functioning adenoma. The STRAS approach allowed a good visualization of intrasphenoidal and intrasellar anatomical landmarks in all cases and no patient needed turbinate resection. No patient died or had neurological deficit. Endocrine remission or control was achieved in 90.5% of hormone-secreting microadenomas and in 84.2% of hormone-secreting macroadenomas. Gross-total resection was achieved for 39 patients (48.8%) of the 80 macroadenomas. Nasal complication rate was very low, with no septal perforation and two epistaxis (1.7%) medically treated. CONCLUSION: The STRAS approach is an elegant approach to the sphenoid sinus that enables a good exposure of the intrasphenoidal anatomical landmarks with a maximal preservation of the nasal mucosa. This approach allows an intrasellar work with great comfort and safety for the surgeon using a two-hand or a four-hand technique.

Adjusting ventilator settings to relieve dyspnoea modifies brain activity in critically ill patients: an electroencephalogram pilot study.

Dyspnoea is frequent and distressing in patients receiving mechanical ventilation, but it is often not properly evaluated by caregivers. Electroencephalographic signatures of dyspnoea have been identified experimentally in healthy subjects. We hypothesized that adjusting ventilator settings to relieve dyspnoea in MV patients would induce EEG changes. This was a first-of-its-kind observational study in a convenience population of 12 dyspnoeic, mechanically ventilated patients for whom a decision to adjust the ventilator settings was taken by the physician in charge (adjustments of pressure support, slope, or trigger). Pre- and post-ventilator adjustment electroencephalogram recordings were processed using covariance matrix statistical classifiers and pre-inspiratory potentials. The pre-ventilator adjustment median dyspnoea visual analogue scale was 3.0 (interquartile range: 2.5-4.0; minimum-maximum: 1-5) and decreased by (median) 3.0 post-ventilator adjustment. Statistical classifiers adequately detected electroencephalographic changes in 8 cases (area under the curve ≥0.7). Previously present pre-inspiratory potentials disappeared in 7 cases post-ventilator adjustment. Dyspnoea improvement was consistent with electroencephalographic changes in 9 cases. Adjusting ventilator settings to relieve dyspnoea produced detectable changes in brain activity. This paves the way for studies aimed at determining whether monitoring respiratory-related electroencephalographic activity can improve outcomes in critically ill patients under mechanical ventilation.

Herpes Simplex Encephalitis Shortly After Surgery for a Secondary Glioblastoma: A Case Report and Review of the Literature.

BACKGROUND: Herpes simplex encephalitis (HSE) and glioblastoma multiforme (GBM) co-occurrence has been described in few cases presenting immunocompromised status related to chemotherapy or chemoradiotherapy. Focal encephalitis over surgical edge of resection occurring shortly after GBM resection is rarely reported, and such infection has never been reported in low-grade glioma with secondary malignant transformation (i.e., secondary GBM). Here, we report a case of HSE misdiagnosed in the early postoperative course following a secondary GBM resection. We also provide a review of the literature about HSE occurring after glioma surgery. CASE DESCRIPTION: We report a case of an acute HSE with a fatal outcome occurring shortly after surgery for a secondary GBM. The patient presented with hyperthermia 12 days after the surgery and was treated with empirical antibiotics. She later suffered from seizure and neurologic deterioration, leading to death despite delayed antiviral administration. Magnetic resonance imaging revealed considerable fluid-attenuated inversion-recovery signal progression at the edge of the surgical resection and polymerase chain reaction amplification of herpes simplex virus (HSV) 1 DNA was positive. CONCLUSIONS: Clinicians should be aware of the existing co-occurrence between HSV infections and GBM during the postoperative course. Cerebrospinal fluid analysis with HSV polymerase chain reaction testing should be promptly undertaken, and some keys clinical elements should justify early empirical treatment, including acyclovir administration. The significant prognostic implication of HSE complicating GBM must raise the attention of neurosurgeon and neuro-oncologist about this entity.

The enigma of multicentric glioblastoma: physiopathogenic hypothesis and discussion about two cases.

Two men were admitted following generalized seizures. Cerebral MRI-scans showed multiple independent enhancing lesions which were bilateral (first case) and unilateral but disseminated to the brainstem (second case). Whole-body CT-scans showed no primaries. Both cases were diagnosed by biopsy as IDH1 wild-type multicentric glioblastoma. Treatment of both was palliative. The natural history of this entity remains matter of debate but 2 genomic analysis strikingly revealed that foci from the same patient were of monoclonal origin. Consistently, these 2 cases could sustain the hypothesis that an anatomical connectivity exists between the different foci of a multicentric glioblastoma.

Outcome of transarterial treatment of dural arteriovenous fistulas with direct or indirect cortical venous drainage.

BACKGROUND AND PURPOSE: Transarterial Onyx embolization is an effective treatment for patients with intracranial dural arteriovenous fistula (DAVF). A study was performed to determine whether the clinical and radiological outcomes after transarterial Onyx treatment were affected by the type of cortical venous drainage (direct vs indirect) of high-grade DAVF. MATERIALS AND METHODS: Between May 2006 and December 2014, demographic data, clinical presentation, angiographic characteristics, and treatment-related outcomes were collected for 54 patients divided into two groups (intracranial DAVF with direct and indirect cortical venous drainage). Continuous variables were compared with the two-tailed t test and categorical variables with the χ2 test. Statistical significance was set at P<0.05. RESULTS: Fifty-two patients (71% with direct and 29% with indirect cortical venous drainage) underwent Onyx embolization. Immediate complete occlusion after treatment was observed in about 55% of patients without between-group difference. During the long-term follow-up, complete angiographic occlusion was achieved in 83% of patients. Specifically, 15 additional patients (40%) in the direct cortical venous drainage group progressed to complete occlusion, but only one (6%) in the indirect cortical venous drainage group. Overall, the rate of complete occlusion was higher in patients with DAVF with direct cortical venous drainage (92%) than in those with DAVF with indirect cortical venous drainage (62.5%) (P=0.01). The rate of permanent treatment-related complications was 4%, mostly related to ischemic events. Overall, 80.5% of patients had a good neurological outcome (modified Rankin Scale score 0-2). CONCLUSIONS: Transarterial Onyx embolization of intracranial high-grade DAVF is safe and effective, particularly for lesions with direct cortical venous drainage.

A Novel Translational Model of Spinal Cord Injury in Nonhuman Primate.

Spinal cord injuries (SCI) lead to major disabilities affecting > 2.5 million people worldwide. Major shortcomings in clinical translation result from multiple factors, including species differences, development of moderately predictive animal models, and differences in methodologies between preclinical and clinical studies. To overcome these obstacles, we first conducted a comparative neuroanatomical analysis of the spinal cord between mice, Microcebus murinus (a nonhuman primate), and humans. Next, we developed and characterized a new model of lateral spinal cord hemisection in M. murinus. Over a 3-month period after SCI, we carried out a detailed, longitudinal, behavioral follow-up associated with in vivo magnetic resonance imaging (1H-MRI) monitoring. Then, we compared lesion extension and tissue alteration using 3 methods: in vivo 1H-MRI, ex vivo 1H-MRI, and classical histology. The general organization and glial cell distribution/morphology in the spinal cord of M. murinus closely resembles that of humans. Animals assessed at different stages following lateral hemisection of the spinal cord presented specific motor deficits and spinal cord tissue alterations. We also found a close correlation between 1H-MRI signal and microglia reactivity and/or associated post-trauma phenomena. Spinal cord hemisection in M. murinus provides a reliable new nonhuman primate model that can be used to promote translational research on SCI and represents a novel and more affordable alternative to larger primates.

Modification of Tracheal Cuff Shape and Continuous Cuff Pressure Control to Prevent Microaspiration in an Ex Vivo Pig Tracheal Two-Lung Model.

OBJECTIVES: Microaspiration of subglottic secretions plays a pivotal role in ventilator-associated pneumonia. Impact of endotracheal tube cuff material and shape on tracheal sealing performance remains debated. The primary objective was to compare the tracheal sealing performance of polyvinyl chloride tapered, cylindrical and spherical cuffs. Secondary objectives were to determine the impact of continuous cuff pressure control on sealing performance and pressure variability. DESIGN: Prospective randomized ex vivo animal study. SETTING: French research laboratory. SUBJECTS: Seventy-two ex vivo pig tracheal two-lung blocks. INTERVENTIONS: Blocks were randomly intubated with cylindrical (n = 26), tapered (n = 24), or spherical (n = 22) polyvinyl chloride endotracheal tube cuffs. Two milliliter of methylene blue were instilled above the cuff to quantify microaspirations, and lungs were ventilated for 2 hours. Continuous cuff pressure control was implemented in 33 blocks. MEASUREMENTS AND MAIN RESULTS: Cuff pressures were continuously recorded, and after 2 hours, a microaspiration score was calculated. Tapered cuffs improved cuff sealing performance compared with spherical cuffs with or without continuous cuff pressure control. Compared with spherical cuffs, tapered cuffs reduced the microaspiration score without and with continuous pressure control by 65% and 72%, respectively. Continuous cuff pressure control did not impact sealing performance. Tapered cuffs generated higher cuff pressures and increased the time spent with overinflation compared with spherical cuffs (median [interquartile range], 77.9% [0-99.8] vs. 0% [0-0.5]; p = 0.03). Continuous cuff pressure control reduced the variability of tapered and spherical cuffs likewise the time spent with overinflation of tapered and cylindrical cuffs. CONCLUSIONS: Polyvinyl chloride tapered cuffs sealing enhanced performance at the cost of an increase in cuff pressure and in time spent with overinflation. Continuous cuff pressure control reduced the variability and normalized cuff pressures without impacting sealing performance.

RNA-Seq Analysis of Microglia Reveals Time-Dependent Activation of Specific Genetic Programs following Spinal Cord Injury.

Neurons have inherent competence to regrow following injury, although not spontaneously. Spinal cord injury (SCI) induces a pronounced neuroinflammation driven by resident microglia and infiltrating peripheral macrophages. Microglia are the first reactive glial population after SCI and participate in recruitment of monocyte-derived macrophages to the lesion site. Both positive and negative influence of microglia and macrophages on axonal regeneration had been reported after SCI, raising the issue whether their response depends on time post-lesion or different lesion severity. We analyzed molecular alterations in microglia at several time-points after different SCI severities using RNA-sequencing. We demonstrate that activation of microglia is time-dependent post-injury but is independent of lesion severity. Early transcriptomic response of microglia after SCI involves proliferation and neuroprotection, which is then switched to neuroinflammation at later stages. Moreover, SCI induces an autologous microglial expression of astrocytic markers with over 6% of microglia expressing glial fibrillary acidic protein and vimentin from as early as 72 h post-lesion and up to 6 weeks after injury. We also identified the potential involvement of DNA damage and in particular tumor suppressor gene breast cancer susceptibility gene 1 (Brca1) in microglia after SCI. Finally, we established that BRCA1 protein is specifically expressed in non-human primate spinal microglia and is upregulated after SCI. Our data provide the first transcriptomic analysis of microglia at multiple stages after different SCI severities. Injury-induced microglia expression of astrocytic markers at RNA and protein levels demonstrates novel insights into microglia plasticity. Finally, increased microglia expression of BRCA1 in rodents and non-human primate model of SCI, suggests the involvement of oncogenic proteins after CNS lesion.

Surgeon's and Patient's Radiation Exposure Through Vertebral Body Cement Augmentation Procedures: A Prospective Multicentric Study of 49 Cases.

OBJECTIVE: Vertebral body cement augmentation as a treatment option for osteoporotic or traumatic fractures has become increasingly popular during the past decade. However, these surgical procedures require numerous fluoroscopic examinations, resulting in high radiation exposure for the patient and the surgical team. The aim of this study was to evaluate the level of radiation exposure of the spine surgeon and the patient during these percutaneous procedures. METHODS: Forty-nine patients admitted for single- or 2-level vertebral compression fracture were prospectively included and treated with vertebral body cement augmentation. For each procedure, radiation dose was measured on the surgeon's whole body, lens, and extremities as well as patient irradiation. Each surgeon wore 2 thermoluminescent dosimeters to measure lens and extremities radiation exposure and 1 electronic personal dosimeter. Patient clinical and surgical data, effective dose to patient, and surgeon were analyzed. RESULTS: Mean operative time was 31.5 ± 11.7 minutes. The average fluoroscopic time was 61.0 ± 27.1 seconds. The average whole-body radiation dose per procedure was 1.4 ± 2.1 µSv. The average equivalent dose to lens and extremities were 44 µSv and 59 µSv, respectively. CONCLUSIONS: Values of radiation doses for surgeon and patient were lower than those reported in the previous literature. The recommended annual dose limit is set to 500 mSv for extremities and 150 mSv for lens. According to our results, the exposure dose to the eye exceeds the annual limit after 3500 procedures. However, there is increasing concern among surgeons about radiation exposure, and there is still a need for solutions as preventive measures.

Tapered-cuff Endotracheal Tube Does Not Prevent Early Postoperative Pneumonia Compared with Spherical-cuff Endotracheal Tube after Major Vascular Surgery: A Randomized Controlled Trial.

BACKGROUND: Patients undergoing major vascular surgery often develop postoperative pneumonia that impacts their outcomes. Conflicting data exist concerning the potential benefit of tapered-shaped cuffs on tracheal sealing. The primary objective of this study was to assess the efficiency of a polyvinyl chloride tapered-cuff endotracheal tube at reducing the postoperative pneumonia rate after major vascular surgery. Secondary objectives were to determine its impact on microaspiration, ventilator-associated pneumonia rate, and inner cuff pressure. METHODS: This prospective randomized controlled study included 109 patients who were randomly assigned to receive either spherical- (standard cuff) or taper-shaped (tapered cuff) endotracheal tubes inserted after anesthesia induction and then admitted to the intensive care unit after major vascular surgery. Cuff pressure was continuously recorded over 5 h. Pepsin and α-amylase concentrations in tracheal aspirates were quantified on postoperative days 1 and 2. The primary outcome was the early postoperative pneumonia frequency. RESULTS: Comparing the tapered-cuff with standard-cuff group, respectively, postoperative pneumonia rates were comparable (42 vs. 44%, P = 0.87) and the percentage (interquartile range) of cuff-pressure time with overinflation was significantly higher (16.1% [1.5 to 50] vs. 0.6% [0 to 8.3], P = 0.01), with a 2.5-fold higher coefficient of variation (20.2 [10.6 to 29.4] vs. 7.6 [6.2 to 10.2], P < 0.001). Although microaspiration frequencies were high, they did not differ between groups. CONCLUSION: For major vascular surgery patients, polyvinyl chloride tapered-cuff endotracheal tubes with intermittent cuff-pressure control did not lower the early postoperative pneumonia frequency and did not prevent microaspiration.

Correlation of in vivo and ex vivo (1)H-MRI with histology in two severities of mouse spinal cord injury.

Spinal cord injury (SCI) is a debilitating neuropathology with no effective treatment. Magnetic resonance imaging (MRI) technology is the only method used to assess the impact of an injury on the structure and function of the human spinal cord. Moreover, in pre-clinical SCI research, MRI is a non-invasive method with great translational potential since it provides relevant longitudinal assessment of anatomical and structural alterations induced by an injury. It is only recently that MRI techniques have been effectively used for the follow-up of SCI in rodents. However, the vast majority of these studies have been carried out on rats and when conducted in mice, the contusion injury model was predominantly chosen. Due to the remarkable potential of transgenic mice for studying the pathophysiology of SCI, we examined the use of both in and ex vivo (1)H-MRI (9.4 T) in two severities of the mouse SCI (hemisection and over-hemisection) and documented their correlation with histological assessments. We demonstrated that a clear distinction between the two injury severities is possible using in and ex vivo (1)H-MRI and that ex vivo MR images closely correlate with histology. Moreover, tissue modifications at a remote location from the lesion epicenter were identified by conventional ex vivo MRI analysis. Therefore, in vivo MRI has the potential to accurately identify in mice the progression of tissue alterations induced by SCI and is successfully implemented by ex vivo MRI examination. This combination of in and ex vivo MRI follow-up associated with histopathological assessment provides a valuable approach for further studies intended to evaluate therapeutic strategies on SCI.

End-tidal carbon dioxide is better than arterial pressure for predicting volume responsiveness by the passive leg raising test.

PURPOSE: In stable ventilatory and metabolic conditions, changes in end-tidal carbon dioxide (EtCO(2)) might reflect changes in cardiac index (CI). We tested whether EtCO(2) detects changes in CI induced by volume expansion and whether changes in EtCO(2) during passive leg raising (PLR) predict fluid responsiveness. We compared EtCO(2) and arterial pulse pressure for this purpose. METHODS: We included 65 patients [Simplified Acute Physiology Score (SAPS) II = 57 ± 19, 37 males, under mechanical ventilation without spontaneous breathing, 15 % with chronic obstructive pulmonary disease, baseline CI = 2.9 ± 1.1 L/min/m(2)] in whom a fluid challenge was decided due to circulatory failure and who were monitored by an expiratory-CO(2) sensor and a PiCCO2 device. In all patients, we measured arterial pressure, EtCO(2), and CI before and after a fluid challenge. In 40 patients, PLR was performed before fluid administration. The PLR-induced changes in arterial pressure, EtCO(2), and CI were recorded. RESULTS: Considering the whole population, the fluid-induced changes in EtCO(2) and CI were correlated (r (2) = 0.45, p = 0.0001). Considering the 40 patients in whom PLR was performed, volume expansion increased CI ≥ 15 % in 21 "volume responders." A PLR-induced increase in EtCO(2) ≥ 5 % predicted a fluid-induced increase in CI ≥ 15 % with sensitivity of 71 % (95 % confidence interval: 48-89 %) and specificity of 100 (82-100) %. The prediction ability of the PLR-induced changes in CI was not different. The area under the receiver-operating characteristic (ROC) curve for the PLR-induced changes in pulse pressure was not significantly different from 0.5. CONCLUSION: The changes in EtCO(2) induced by a PLR test predicted fluid responsiveness with reliability, while the changes in arterial pulse pressure did not.