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Regional cerebrovascular reactivity (rCVR) is highly variable in the human brain as measured by blood oxygenation level-dependent (BOLD) MRI to changes in both end-tidal CO 2 and O 2 .We examined awake participants under carefully controlled end-tidal gas concentrations to assess how regional CVR changes may present with end-tidal gas changes seen commonly with anaesthesia.Observational study.Tertiary care centre, Winnipeg, Canada. The imaging for the study occurred in 2019.Twelve healthy adult subjects.Cerebral BOLD response was studied under two end-tidal gas paradigms. First end-tidal oxygen (ETO 2 ) maintained stable whereas ETCO 2 increased incrementally from hypocapnia to hypercapnia (CO 2 ramp); second ETCO 2 maintained stable whereas ETO 2 increased from normoxia to hyperoxia (O 2 ramp). BOLD images were modeled with end-tidal gas sequences split into two equal segments to examine regional CVR.The voxel distribution comparing hypocapnia to mild hypercapnia and mild hyperoxia (mean F I O 2 = 0.3) to marked hyperoxia (mean F I O 2 = 0.7) were compared in a paired fashion ( P 0.005 to reach threshold for voxel display). Additionally, type analysis was conducted on CO 2 ramp data. This stratifies the BOLD response to the CO 2 ramp into four categories of CVR slope based on segmentation (type A; +/+slope: normal response, type B +/-, type C -/-: intracranial steal, type D -/+.) Types B to D represent altered responses to the CO 2 stimulus.Differential regional responsiveness was seen for both end-tidal gases. Hypocapnic regional CVR was more marked than hypercapnic CVR in 0.3% of voxels examined ( P 0.005, paired comparison); the converse occurred in 2.3% of voxels. For O 2 , mild hyperoxia had more marked CVR in 0.2% of voxels compared with greater hyperoxia; the converse occurred in 0.5% of voxels. All subjects had altered regional CO 2 response based on Type Analysis ranging from 4 ± 2 to 7 ± 3% of voxels.In awake subjects, regional differences and abnormalities in CVR were observed with changes in end-tidal gases common during the conduct of anaesthesia. On the basis of these findings, consideration could be given to minimising regional CVR fluctuations in patients-at-risk of neurological complications by tighter control of end-tidal gases near the individual's resting values.

Anesthesia is associated with alterations in end-tidal (ET) respiratory gases from the awake state. These alterations result in marked vasoactive changes in regional cerebral blood flow (rCBF). Altered regional cerebrovascular reactivity (rCVR) is linked to neurologic dysfunction. We examined these differences in reactivity from prior work by focusing on the ratio of vasoconstriction with hyperoxia/hypocapnia (HO/hc):vasodilation with hypercapnia (HC) using magnetic resonance imaging pseudo-continuous arterial spin labelling (pCASL) to measure rCBF and compare rCVR The distribution and magnitude of these ratios could provide insights into rCBF during clinical anesthesia and inform future research into the origins of postoperative delirium (POD). Ten healthy subjects underwent cerebral blood flow (CBF) studies using pCASL with computer-controlled delivery of ET gases to assess flow effects of hyperoxia, hypercapnia, and hyperoxia/hypocapnia as part of a larger study into cerebrovascular reactivity. The vasoconstrictor stimulus was compared with the vasodilator stimulus by the ratio HO/hc:HC. Hyperoxia minimally decreased whole brain CBF by − 0.6%/100 mm Hg increase in ETO2. Hypercapnia increased CBF by +4.6%/mm Hg carbon dioxide (CO2) and with HO/hc CBF decreased by − 5.1%/mm Hg CO2. The brain exhibited markedly different rCVR—regional HO/hc:HC ratios varied from 7.2:1 (greater response to vasoconstriction) to 0.49:1 (greater response to vasodilation). Many of the ratios greater than 1, where vasoconstriction predominated, were seen in regions associated with memory, cognition, and executive function, including the entorhinal cortex, hippocampus, parahippocampus, and dorsolateral prefrontal cortex. In awake humans, marked rCBF changes occurred with alterations in ET respiratory gases common under anesthesia. Such heterogeneous reactivity may be relevant to future studies to identify those at risk of POD.

Concussion imaging research has primarily focused on neuronal disruption with lesser emphasis directed toward vascular dysfunction. However, blood flow metrics may be more sensitive than measures of neuronal integrity. Vascular dysfunction can be assessed by measuring cerebrovascular reactivity (CVR)-the change in cerebral blood flow per unit change in vasodilatory stimulus. CVR metrics, including speed and magnitude of flow responses to a standardized well-controlled vasoactive stimulus, are potentially useful for assessing individual subjects following concussion given that blood flow dysregulation is known to occur with traumatic brain injury. We assessed changes in CVR metrics to a standardized vasodilatory stimulus during the acute phase of concussion. Using a case control design, 20 concussed participants and 20 healthy controls (HCs) underwent CVR assessment measuring blood oxygen-level dependent (BOLD) magnetic resonance imaging using precise changes in end-tidal partial pressure of CO2 (PETCO2). Metrics were calculated for the whole brain, gray matter (GM), and white matter (WM) using sex-stratification. A leave-one-out receiver operating characteristic (ROC) analysis classified concussed from HCs based on CVR metrics. CVR magnitude was greater and speed of response faster in concussed participants relative to HCs, with WM showing higher classification accuracy compared with GM. ROC analysis for WM-CVR metrics revealed an area under the curve of 0.94 in males and 0.90 in females for speed and magnitude of response respectively. These greater than normal responses to a vasodilatory stimulus warrant further investigation to compare the predictive ability of CVR metrics against structural injury metrics for diagnosis and prognosis in acute concussion.

Anesthesia is associated with alterations in end-tidal (ET) respiratory gases from the awake state. These alterations result in marked vasoactive changes in regional cerebral blood flow (rCBF). Altered regional cerebrovascular reactivity (rCVR) is linked to neurologic dysfunction. We examined these differences in reactivity from prior work by focusing on the ratio of vasoconstriction with hyperoxia/hypocapnia (HO/hc):vasodilation with hypercapnia (HC) using magnetic resonance imaging pseudo-continuous arterial spin labelling (pCASL) to measure rCBF and compare rCVR The distribution and magnitude of these ratios could provide insights into rCBF during clinical anesthesia and inform future research into the origins of postoperative delirium (POD).Ten healthy subjects underwent cerebral blood flow (CBF) studies using pCASL with computer-controlled delivery of ET gases to assess flow effects of hyperoxia, hypercapnia, and hyperoxia/hypocapnia as part of a larger study into cerebrovascular reactivity. The vasoconstrictor stimulus was compared with the vasodilator stimulus by the ratio HO/hc:HC.Hyperoxia minimally decreased whole brain CBF by - 0.6%/100 mm Hg increase in ETOIn awake humans, marked rCBF changes occurred with alterations in ET respiratory gases common under anesthesia. Such heterogeneous reactivity may be relevant to future studies to identify those at risk of POD.RéSUMé: OBJECTIF: L’anesthésie est associée à des altérations des gaz respiratoires télé-expiratoires par rapport à l’état d’éveil. Ces altérations entraînent des changements vasoactifs marqués dans le débit sanguin cérébral régional (DSCR). Une altération de la réactivité cérébrovasculaire régionale (rCVR) est liée au dysfonctionnement neurologique. Nous avons examiné ces différences de réactivité dans des études antérieures en nous concentrant sur le rapport entre la vasoconstriction et l’hyperoxie/hypocapnie (HO/hc):vasodilatation et l’hypercapnie (HC), en utilisant une technique d’imagerie par résonance magnétique dite pCASL (pour pseudo-continuous arterial spin labelling) pour mesurer le DSCR et comparer la rCVR. La distribution et l’ampleur de ces rapports pourraient fournir des renseignements concernant le DSCR pendant l’anesthésie clinique et éclairer la recherche future sur les origines du delirium postopératoire (DPO). MéTHODE: Dix volontaires sains ont subi des études de débit sanguin cérébral (DSC) à l’aide d’une pCASL avec un contrôle géré par ordinateur des gaz télé-expiratoires pour évaluer les effets sur le débit de l’hyperoxie, de l’hypercapnie, et de l’hyperoxie/hypocapnie dans le cadre d’une plus grande étude sur la réactivité cérébrovasculaire. Le stimulus vasoconstricteur a été comparé au stimulus vasodilatateur par le rapport de HO/hc:HC. RéSULTATS: L’hyperoxie a diminué de façon minimale le DSC du cerveau entier de − 0,6 %/100 mmHg en ETO

There is growing interest in developing magnetic resonance imaging (MRI) biomarkers of brain connectivity from resting-state functional (rs-fMRI) and diffusion tensor imaging (DTI) to aid in the diagnosis and management of patients with mild traumatic brain injury (mTBI). To determine whether early MRI biomarkers of brain connectivity are useful in predicting outcome after mTBI, we conducted a systematic review using the following inclusion criteria: 1) patients aged16 years with mTBI, 2) MRI performed during the first month post-injury, 3) outcome measure available, 4) control group, and 5) original article published in a peer-reviewed journal. Of the 1351 citations identified, 14 studies met inclusion criteria (5 rs-fMRI and 10 DTI; 680 patients with mTBI vs. 436 controls) including those where MRI was performed from12 h to 1 month post-injury. The most common clinical outcome measure used in these studies was symptom burden using the Rivermead Post-Concussion Questionnaire. The most frequently studied brain connectivity MRI biomarkers were global functional connectivity, default-mode network, and fractional anisotropy (FA). Despite the scant evidence and considerable methodological heterogeneity observed among studies, we conclude that brain connectivity MRI biomarkers obtained within 1 month of injury may be potentially useful in predicting outcome in mTBI. Further longitudinal studies are needed to evaluate the effect of mTBI on MRI-based brain connectivity biomarkers and examine how incorporation of these tests can inform the clinical care of individual mTBI patients.

OBJECTIVE Hemifacial spasm (HFS) is a cranial nerve hyperactivity disorder characterized by unique neurophysiological features, although the underlying pathophysiology remains disputed. In this study, the authors compared the effects of desflurane on facial motor evoked potentials (MEPs) from the spasm and nonspasm sides of patients who were undergoing microvascular decompression (MVD) surgery to test the hypothesis that HFS is associated with a central elevation of facial motor neuron excitability. METHODS Facial MEPs were elicited in 31 patients who were undergoing MVD for HFS and were administered total intravenous anesthesia (TIVA) with or without additional desflurane, an inhaled anesthetic known to centrally suppress MEPs. All measurements were completed before dural opening while a consistent mean arterial blood pressure was maintained and electroencephalography was performed. The activation threshold voltage and mean amplitudes of the MEPs from both sides of the face were compared. RESULTS There was a significantly lower mean activation threshold of facial MEPs on the spasm side than on the nonspasm side (mean ± SD 162.9 ± 10.1 vs 198.3 ± 10.1 V, respectively; p = 0.01). In addition, MEPs were also elicited more readily when single-pulse transcranial electrical stimulation was used on the spasm side (74% vs 31%, respectively; p = 0.03). Although desflurane (1 minimum alveolar concentration) suppressed facial MEPs on both sides, the suppressive effects of desflurane were less on the spasm side than on the nonspasm side (59% vs 79%, respectively; p = 0.03), and M waves recorded from the mentalis muscle remained unchanged, which indicates that desflurane did not affect the peripheral facial nerve or neuromuscular junction. CONCLUSIONS Centrally acting inhaled anesthetic agents can suppress facial MEPs and therefore might interfere with intraoperative monitoring. The elevated motor neuron excitability and differential effects of desflurane between the spasm and nonspasm sides support a mechanism of central pathophysiology in HFS. Clinical trial registration no.: B2012:099 (clinicaltrials.gov)

Background Mechanical ventilation to alter and improve respiratory gases is a fundamental feature of critical care and intraoperative anesthesia management. The range of inspired O2 and expired CO2 during patient management can significantly deviate from values in the healthy awake state. It has long been appreciated that hyperoxia can have deleterious effects on organs, especially the lung and retina. Recent work shows intraoperative end-tidal (ET) CO2 management influences the incidence of perioperative neurocognitive disorder (POND). The interaction of O2 and CO2 on cerebral blood flow (CBF) and oxygenation with alterations common in the critical care and operating room environments has not been well studied. Methods We examine the effects of controlled alterations in both ET O2 and CO2 on cerebral blood flow (CBF) in awake adults using blood oxygenation level-dependent (BOLD) and pseudo-continuous arterial spin labeling (pCASL) MRI. Twelve healthy adults had BOLD and CBF responses measured to alterations in ET CO2 and O2 in various combinations commonly observed during anesthesia. Results Dynamic alterations in regional BOLD and CBF were seen in all subjects with expected and inverse brain voxel responses to both stimuli. These effects were incremental and rapid (within seconds). The most dramatic effects were seen with combined hyperoxia and hypocapnia. Inverse responses increased with age suggesting greater risk. Conclusions Human CBF responds dramatically to alterations in ET gas tensions commonly seen during anesthesia and in critical care. Such alterations may contribute to delirium following surgery and under certain circumstances in the critical care environment. Trial registration ClincialTrials.gov NCT02126215 for some components of the study. First registered April 29, 2014.

OBJECT A neuroimaging assessment tool to visualize global and regional impairments in cerebral blood flow (CBF) and cerebrovascular responsiveness in individual patients with concussion remains elusive. Here the authors summarize the safety, feasibility, and results of brain CO2 stress testing in adolescents with postconcussion syndrome (PCS) and healthy controls. METHODS This study was approved by the Biomedical Research Ethics Board at the University of Manitoba. Fifteen adolescents with PCS and 17 healthy control subjects underwent anatomical MRI, pseudo-continuous arterial spin labeling MRI, and brain stress testing using controlled CO2 challenge and blood oxygen level–dependent (BOLD) MRI. Post hoc processing was performed using statistical parametric mapping to determine voxel-by-voxel regional resting CBF and cerebrovascular responsiveness of the brain to the CO2 stimulus (increase in BOLD signal) or the inverse (decrease in BOLD signal). Receiver operating characteristic (ROC) curves were generated to compare voxel counts categorized by control (0) or PCS (1). RESULTS Studies were well tolerated without any serious adverse events. Anatomical MRI was normal in all study participants. No differences in CO2 stimuli were seen between the 2 participant groups. No group differences in global mean CBF were detected between PCS patients and healthy controls. Patient-specific differences in mean regional CBF and CO2 BOLD responsiveness were observed in all PCS patients. The ROC curve analysis for brain regions manifesting a voxel response greater than and less than the control atlas (that is, abnormal voxel counts) produced an area under the curve of 0.87 (p < 0.0001) and 0.80 (p = 0.0003), respectively, consistent with a clinically useful predictive model. CONCLUSIONS Adolescent PCS is associated with patient-specific abnormalities in regional mean CBF and BOLD cerebrovascular responsiveness that occur in the setting of normal global resting CBF. Future prospective studies are warranted to examine the utility of brain MRI CO2 stress testing in the longitudinal assessment of acute sports-related concussion and PCS.

A signature EMG feature of hemifacial spasm (HFS) is the lateral spread response (LSR). Desflurane is a common anesthetic with potent effects on synaptic transmission. We tested the hypothesis that the LSR is mediated by corticobulbar components by comparing the LSR during total intravenous anesthesia (TIVA) or TIVA plus desflurane during microvascular decompression (MVD) surgery.22 HFS patients undergoing MVD surgery participated in this prospective study. The LSR data was recorded from the o. oculi, o. oris and mentalis muscles prior to opening dura. LSR onset latencies and amplitudes were determined under TIVA and TIVA/desflurane (0.5 and 1MAC). Facial muscle LSRs and EEG were analyzed.Desflurane (1MAC) significantly decreased the LSR amplitude in all 3 facial muscles (p0.01). Pooled LSR data from all facial muscles showed desflurane inhibited the LSR amplitude by 43% compared to TIVA (p0.001). No effects on the latency of the LSR or on EEG state were observed.LSR inhibition by desflurane suggests a central mechanism involvement in the genesis of this signature HFS response.This study demonstrates that facial nerve vascular compression and plastic changes within the CNS are part of the pathophysiology of HFS.

Evidence of anesthetic neurotoxicity is unequivocal when studied in animal models. These findings have translated poorly to the clinical domain when equated to postoperative delirium (POD) in adults and postoperative cognitive dysfunction (POCD) in either children or the elderly. In this perspective, we examine various reasons for the differences between animal modeling of neurotoxicity and the clinical situation of POD and POCD and make suggestions as to potential directions for ongoing research. We hypothesize that the animal anesthetic neurotoxicity models are limited, in part, due to failed scaling correction of physiological time. We posit that important insights into POCD in children and adults may be gleaned from studies in adults examining alterations in perioperative management designed to limit POD. In this way, POD may be more useful as the proxy for POCD rather than neuronal dropout or behavioral abnormalities that have been used in animal models but which may not be proxies for the human condition. We argue that it is time to move beyond animal models of neurotoxicity to directly examine these problems in well-conducted clinical trials with comprehensive preoperative neuropsychometric and psychiatric testing, high fidelity intraoperative monitoring of physiological parameters during the anesthetic course and postoperative assessment of subthreshold and full classification of POD. In this manner, we can "model ourselves" to better understand these important and poorly understood conditions.

Cerebral desaturation occurs frequently in patients undergoing one-lung ventilation for thoracic surgery. The mechanism of this desaturation is unclear regarding its etiology. The objective of this study was to investigate whether or not decreases in cerebral oxygen saturation associated with one-lung ventilation were a consequence of decreased cardiac output. A blinded observational study was conducted in 23 patients undergoing one-lung ventilation with thoracic surgery. Eighteen patients completed the study. Cerebral oxygen saturation was monitored using near-infrared spectroscopy (FORE-SIGHT® monitor). Invasive blood pressure was monitored and hemodynamic variables were interrogated using the FloTrac® system. Anesthesia was maintained with sevoflurane with a F i O2 of 1.0. Post-hoc analysis involved a comparison between baseline and integrated changes in cerebral saturation, heart rate, stroke index, cardiac index, and stroke volume variability. All patients showed cerebral desaturation from a baseline of two-lung ventilation in the lateral decubitus position following institution of one-lung ventilation. The cardiac index was stable at these times, but with one-lung ventilation, the heart rate decreased and the stroke index increased to maintain a stable product. The integral of heart rate × time was inversely correlated with the integral of cerebral desaturation × time (linear regression analysis; P = 0.02; (df) = 16)). Cerebral oxygen desaturation was universal during one-lung ventilation in this study. There was no correlation between cerebral desaturation and cardiac output or other hemodynamic variables.

Background Advanced neuroimaging studies in concussion have been limited to detecting group differences between concussion patients and healthy controls. In this small pilot study, we used brain magnetic resonance imaging (MRI) CO2 stress testing to longitudinally assess cerebrovascular responsiveness (CVR) in individual sports-related concussion (SRC) patients. Methods Six SRC patients (three males and three females; mean age = 15.7, range = 15–17 years) underwent longitudinal brain MRI CO2 stress testing using blood oxygen level-dependent (BOLD) MRI and model-based prospective end-tidal CO2 targeting under isoxic conditions. First-level and second-level comparisons were undertaken using statistical parametric mapping (SPM) to score the scans and compare them to an atlas of 24 healthy control subjects. Results All tests were well tolerated and without any serious adverse events. Anatomical MRI was normal in all study participants. The CO2 stimulus was consistent between the SRC patients and control subjects and within SRC patients across the longitudinal study. Individual SRC patients demonstrated both quantitative and qualitative patient-specific alterations in CVR (p

Science and medicine have been beset by an increasing incidence of fraud detected in academic research. Historically, academic fraud involving either ethical and/or scientific misconduct has often been associated with high profile journals. A number of these high profile cases have involved anesthesiologists. One well-publicized case of academic fraud resulted in the imprisonment of anesthesiologist, Dr. Scott Reuben, who was at the centre of more than 20 falsified studies in multimodal pain therapy. More recently, a joint statement from the editors-inchief of 16 anesthesia, perioperative, and critical care journals has outlined the group retraction of 88 articles authored or co-authored by another anesthesiologist, Dr. Joachim Boldt. The large number of article retractions over the past several years brings into question whether there is a specialty-related propensity for anesthesiologists to be tempted to commit academic fraud, or are the recent exposures merely a statistical blip? Steen argues convincingly that medical fraud is increasing in general. However, he also notes that Dr. Reuben was responsible for 25% of the fraudulent papers retracted in 2009 (a total of 13 of his papers that year) as listed on PubMed. Unfortunately, given the number of retractions attributable to Dr. Boldt (a number likely to rise), our specialty will remain in the limelight. There are many different forms of academic fraud, ranging from text or data plagiarism to ghostwriting, to data and image manipulation, to data and image fabrication. The first problem, text plagiarism, is now being addressed very actively as new and more powerful software programs compare submitted manuscript text to existing published works both in journals and theses. In the case of Dr. Reuben’s articles, the retractions exemplify the more egregious examples relating to data manipulation and fabrication. In the case of Dr. Boldt, the 88 articles identified on the editors’ joint statement were retracted due to lack of evidence of Institutional Research Ethics Board approval, which constitutes ethical misconduct in research. There are ongoing investigations to assess the scientific integrity of these articles, since the first article retraction was on the basis of data falsification. In view of the above, it is important to consider the risk that academic fraud may impose on anesthesia, to contemplate why our specialty may be at greater risk in some circumstances, and to suggest potential solutions.

Poor outcome in patients with cerebral vasospasm following subarachnoid hemorrhage remains a serious clinical problem. The current management with focus on the cerebrovascular constriction accounts for the use of “triple-H” therapy (hypertension, hypervolemia, and hemodilution) to enhance cerebral blood flow through constricted vessels. Recent work suggests that spreading depression (a stereotypical response of cerebral cortical tissue to noxious stimuli with subsequent oligemic blood flow) occurs in patients with cerebral vasospasm. A narrative review was conducted to examine the relationship between spreading depression and subarachnoid hemorrhage and to identify the anesthetic effects on the propagation of spreading depression. Following review of the literature, an underlying mechanism is advanced that cerebral vasospasm is not primarily a problem of the cerebral vasculature but a consequence of glial cell dysfunction following spreading depression – a glial-centric cause for vasospasm. Such a mechanism for vasospasm becomes manifest when spreading depression waves transition to peri-infarct depolarization waves – with protracted ischemic blood flow in compromised tissue. The extracellular microenvironment with high potassium and low nitric oxide tension can account for conducting vessel narrowing. The implication for clinical management is discussed supposing glial cell dysfunction is an underlying mechanism responsible for the vascular spasm.

Obstetrical risk is increased with maternal obesity. This prospective study was designed to simultaneously evaluate the outcomes in obese parturients and their newborns.Patients with a body mass index (BMI)or =35 were prospectively identified and compared to an equal number of normal weight parturients. Maternal and neonatal outcome measures were compared for the peripartum and neonatal period.We identified 580 obese parturients over a 6 month period and compared them to an equal number of normal weight parturients. The incidence of obesity in this population was 23%. Obesity was associated with increased rates of hypertension, diabetes, and cesarean section. Obese patients were more likely to develop postpartum complications. Neonatal outcomes were compared for infantsor =37 weeks gestation excluding multiple births (496 neonates in the obese group and 520 in the control group). The neonates of obese parturients were more likely to be macrosomic, have 1-minute Apgar scores ofor =7.0 and require admission to a special care unit. Sub-group analysis showed that negative outcomes for parturients and their neonates correlated with increasing BMI. Neonates born to obese diabetic parturients had the highest risk of poor outcomes.Maternal obesity confers increased risks for both the parturient and their newborn.

Renal injury is common after open-heart surgery. Cardiopulmonary bypass contributes to the problem. We compared conventional nonpulsatile perfusion (NP) to biologically variable perfusion (BVP), which uses a computer controller to restore physiological beat-to-beat variability to roller pump flow. We hypothesized BVP would decrease renal injury after deep hypothermic circulatory arrest.Pigs were randomly assigned to either BVP (n = 9) or NP (n = 9), cooled, arrested at 18 degrees C (1 hour), reperfused, and rewarmed and maintained normothermic (3 hours). Additional pigs had NP for a similar time as above, but without circulatory arrest (n = 3), or were sham-treated without bypass (n = 3). Hemodynamics, acid-base status, temperature, and urine volumes were measured. Urinary enzyme markers of tubular injury were compared post-hoc for gamma glutamyl transpeptidase, alkaline phosphatase, and glutathione S-transferase and by urine proteomics using mass spectrometry.Urine output at 1 hour after arrest was 250 +/- 129 mL with BVP versus 114 +/- 66 mL with NP (p0.02). All three renal enzyme markers were higher with NP after arrest compared with BVP. In animals on bypass without arrest or those sham-treated, no elevations were seen in renal enzymes. Urine proteomics revealed abnormal proteins, persisting longer with NP. Biologically variable perfusion decreased cooling to 21.0 +/- 9.0 minutes versus 31.7 +/- 7.5 minutes (p0.002), and decreased rewarming to 22.1 +/- 3.9 minutes versus 31.2 +/- 5.1 minutes (p0.002).Biologically variable perfusion improved urine output, decreased enzymuria, and attenuated mass spectrometry urine protein signal with more rapid temperature changes. This strategy could potentially shorten bypass duration and may decrease renal tubular injury with deep hypothermic circulatory arrest.

Background Hypoxemia is common during one-lung ventilation (OLV). Atelectasis contributes to the problem. Biologically variable ventilation (BVV), using microprocessors to reinstitute physiologic variability to respiratory rate and tidal volume, has been shown to be advantageous over conventional monotonous control mode ventilation (CMV) in improving oxygenation during the period of lung reinflation after OLV in an experimental model. Here, using a porcine model, the authors compared BVV with CMV during OLV to assess gas exchange and respiratory mechanics. Methods Eight pigs (25-30 kg) were studied in each of two groups. After induction of anesthesia-tidal volume 12 ml/kg with CMV and surgical intervention-tidal volume was reduced to 9 ml/kg. OLV was initiated with an endobronchial blocker, and the animals were randomly allocated to either continue CMV or switch to BVV for 90 min. After OLV, a recruitment maneuver was undertaken, and both lungs were ventilated for a further 60 min. At predetermined intervals, hemodynamics, respiratory gases (arterial, venous, and end-tidal samples) and mechanics (airway pressures, static and dynamic compliances) were measured. Derived indices (pulmonary vascular resistance, shunt fraction, and dead space ventilation) were calculated. Results By 15 min of OLV, arterial oxygen tension was greater in the BVV group (group x time interaction, P = 0.003), and shunt fraction was lower with BVV from 30 to 90 min (group effect, P = 0.0004). From 60 to 90 min, arterial carbon dioxide tension was lower with BVV (group x time interaction, P = 0.0001) and dead space ventilation was less from 60 to 90 min (group x time interaction, P = 0.0001). Static compliance was greater by 60 min of BVV and remained greater during return to ventilation of both lungs (group effect, P = 0.0001). Conclusions In this model of OLV, BVV resulted in superior gas exchange and respiratory mechanics when compared with CMV. Improved static compliance persisted with restoration of two-lung ventilation.

Mechanical ventilators breathe for you when you cannot or when your lungs are too sick to do their job. Most ventilators monotonously deliver the same-sized breaths, like clockwork; however, healthy people do not breathe this way. This has led to the development of a biologically variable ventilator—one that incorporates noise. There are indications that such a noisy ventilator may be beneficial for patients with very sick lungs. In this paper we use a probabilistic argument, based on Jensen's inequality, to identify the circumstances in which the addition of noise may be beneficial and, equally important, the circumstances in which it may not be beneficial. Using the local convexity of the relationship between airway pressure and tidal volume in the lung, we show that the addition of noise at low volume or low pressure results in higher mean volume (at the same mean pressure) or lower mean pressure (at the same mean volume). The consequence is enhanced gas exchange or less stress on the lungs, both clinically desirable. The argument has implications for other life support devices, such as cardiopulmonary bypass pumps. This paper illustrates the benefits of research that takes place at the interface between mathematics and medicine.

BackgroundThere is a real need for quantifiable neuro-imaging biomarkers in concussion. Here we outline a brain BOLD-MRI CO2 stress test to assess the condition.MethodsThis study was approved by the REB at the University of Manitoba. A group of volunteers without prior concussion were compared to post-concussion syndrome (PCS) patients--both symptomatic and recovered asymptomatic. Five 3-minute periods of BOLD imaging at 3.0 T were studied--baseline 1 (BL1--at basal CO2 tension), hypocapnia (CO2 decreased ∼5 mmHg), BL2, hypercapnia (CO2 increased ∼10 mmHg) and BL3. Data were processed using statistical parametric mapping (SPM) for 1st level analysis to compare each subject's response to the CO2 stress at the p = 0.001 level. A 2nd level analysis compared each PCS patient's response to the mean response of the control subjects at the p = 0.05 level.ResultsWe report on 5 control subjects, 8 symptomatic and 4 asymptomatic PCS patients. Both increased and decreased response to CO2 was seen in all PCS patients in the 2nd level analysis. The responses were quantified as reactive voxel counts: whole brain voxel counts (2.0±1.6%, p = 0.012 for symptomatic patients for CO2 response < controls and 3.0±5.1%, p = 0.139 for CO2 response > controls: 0.49±0.31%, p = 0.053 for asymptomatic patients for CO2 response < controls and 4.4±6.8%, p = 0.281 for CO2 response > controls).ConclusionsQuantifiable alterations in regional cerebrovascular responsiveness are present in concussion patients during provocative CO2 challenge and BOLD MRI and not in healthy controls. Future longitudinal studies must aim to clarify the relationship between CO2 responsiveness and individual patient symptoms and outcomes.

Biologically variable mechanical ventilation (V˙bv)—using a computer-controller to mimic the normal variability in spontaneous breathing—improves gas exchange in a model of severe lung injury (Lefevre, G. R., S. E. Kowalski, L. G. Girling, D. B. Thiessen, W. A. C. Mutch. Am. J. Respir. Crit. Care Med. 1996;154:1567–1572). Improved oxygenation with V˙bv, in the face of alveolar collapse, is thought to be due to net volume recruitment secondary to the variability or increased noise in the peak inspiratory airway pressures (Ppaw). Biologically variable noise can be modeled as an inverse power law frequency distribution (y ∝ 1/fa) (West, B. J., M. Shlesinger. Am. Sci. 1990;78:40–45). In a porcine model of atelectasis—right lung collapse with one-lung ventilation—we studied if V˙bv (n = 7) better reinflates the collapsed lung compared with conventional monotonously regular control mode ventilation (V˙c; n = 7) over a 5-h period. We also investigated the influence of sigh breaths with V˙c (V˙s; n = 8) with this...

Background . Conventional pulsatile (CP) roller pump cardiopulmonary bypass (CPB) was compared to computer controlled biologically variable pulsatile (BVP) bypass designed to return beat-to-beat variability in rate and pressure with superimposed respiratory rhythms. Jugular venous O 2 saturation (SjvO 2 ) below 50% during rewarming from hypothermia was compared for the two bypass techniques. A SjvO 2 less than 50% during rewarming is correlated with cognitive dysfunction in humans. Methods . Pigs were placed on CPB for 3 hours using a membrane oxygenator with α-stat acid base management and arterial filtration. After apulsatile normothermic CPB was initiated, animals were randomized to CP (n = 8) or BVP (roller pump speed adjusted by an average of 2.9 voltage output modulations/second; n=8), then cooled to a nasopharyngeal temperature of 28°C. During rewarming to stable normothermia, SjvO 2 was measured at 5 minute intervals. The mean and cumulative area for SjvO 2 less than 50% was determined. Results . No between group difference in temperature existed during hypothermic CPB or during rewarming. Mean arterial pressure, arterial partial pressure O 2 , and arterial partial pressure CO 2 did not differ between groups. The hemoglobin concentration was within 0.4 g/dL between groups at all time periods. The range of systolic pressure was greater with BVP (41 ± 18 mm Hg) than with CP (12 ± 4 mm Hg). A greater mean and cumulative area under the curve for SjvO 2 less than 50% was seen with CP (82 ± 96 versus 3.6% ± 7.3% · min, p = 0.004; and 983 ± 1158 versus 42% ± 87% · min; p = 0.004, Wilcoxon 2-sample test). Conclusions . Computer-controlled BVP resulted in significantly greater SjvO 2 during rewarming from hypothermic CPB. Both mean and cumulative area under the curve for SjvO 2 less than 50% exceeded a ratio of 20 to 1 for CP versus BVP. Cerebral oxygenation is better preserved during rewarming from moderate hypothermia with bypass that returns biological variability to the flow pattern.

Background . Conventional roller pump apulsatile cardiopulmonary bypass (CPB) was compared with computer-controlled pulsatile bypass, which was designed to recreate biological variability (return of beat-to-beat variability in rate and pressure with superimposed respiratory rhythms). The degree of jugular venous oxygen saturation (SjvO 2 ) less than 50% during rewarming from hypothermic CPB was compared for the two bypass techniques. An SjvO 2 less than 50% during rewarming from hypothermic CPB is correlated with cognitive dysfunction in humans. Methods . Pigs were placed on CPB for 3 hours using a membrane oxygenator with alpha-stat acid-base management and arterial filtration. After baseline measurements and normothermic CPB, the animals were randomized to apulsatile CPB (n = 12) or computer-controlled pulsatile CPB (roller pump speed adjusted by an average of 2.9 voltage output modulations/s; n=12). The animals were then cooled to a nasopharyngeal temperature of 28°C. During rewarming to stable normothermic temperatures, SjvO 2 was measured at 5-minute intervals. The mean and cumulative areas for an SjvO 2 less than 50% were determined for all animals. Results . No between-group differences in temperature were noted during hypothermic CPB or during rewarming. The rate of rewarming was not different between groups. Mean arterial pressure, partial pressure of oxygen in arterial blood, and partial pressure of carbon dioxide in arterial blood also did not differ between groups. The hemoglobin concentration was within 0.4 g/dL between groups at all time periods. Mean pulse pressure was 10.0 ± 4.8 mm Hg in the apulsatile CPB group and 20.7 ± 5.2 mm Hg in the pulsatile CPB group ( p = 0.0002; unpaired t test). Markedly greater mean and cumulative areas under the curve for SjvO 2 less than 50% were seen with apulsatile CPB (164 ± 209 versus 1.9 ± 3.6% · min, p = 0.021; and 1,796 ± 2,263 versus 23 ± 45% · min, p = 0.020, respectively). Conclusions . Computer-controlled pulsatile CPB was associated with significantly greater SjvO 2 during rewarming from hypothermic CPB. Both the mean and cumulative areas under the curve for SjvO 2 less than 50% exceeded a ratio of 75:1 for apulsatile versus computer-controlled pulsatile CPB. These experiments suggest that cerebral oxygenation was better preserved during rewarming from moderate hypothermia with computer-controlled pulsatile CPB, which returned biologic variability to the flow pattern.

BackgroundMonitoring cerebral saturation is increasingly seen as an aid to management of patients in the operating room and in neurocritical care. How best to manipulate cerebral saturation is not fully known. We examined cerebral saturation with graded changes in carbon dioxide tension while isoxic and with graded changes in oxygen tension while isocapnic.Methodology/principal findingsThe study was approved by the Research Ethics Board of the University Health Network at the University of Toronto. Thirteen studies were undertaken in healthy adults with cerebral oximetry by near infrared spectroscopy. End-tidal gas concentrations were manipulated using a model-based prospective end-tidal targeting device. End-tidal carbon dioxide was altered ±15 mmHg from baseline in 5 mmHg increments with isoxia (clamped at 110±4 mmHg). End-tidal oxygen was changed to 300, 400, 500, 80, 60 and 50 mmHg under isocapnia (37±2 mmHg). Twelve studies were completed. The end-tidal carbon dioxide versus cerebral saturation fit a linear relationship (R(2) = 0.92±0.06). The end-tidal oxygen versus cerebral saturation followed log-linear behaviour and best fit a hyperbolic relationship (R(2) = 0.85±0.10). Cerebral saturation was maximized in isoxia at end-tidal carbon dioxide of baseline +15 mmHg (77±3 percent). Cerebral saturation was minimal in isocapnia at an end-tidal oxygen tension of 50 mmHg (61±3 percent). The cerebral saturation during normoxic hypocapnia was equivalent to normocapnic hypoxia of 60 mmHg.Conclusions/significanceHypocapnia reduces cerebral saturation to an extent equivalent to moderate hypoxia.

Background An impaired vascular response in the brain regionally may indicate reduced vascular reserve and vulnerability to ischemic injury. Changing the carbon dioxide (CO(2)) tension in arterial blood is commonly used as a cerebral vasoactive stimulus to assess the cerebral vascular response, changing cerebral blood flow (CBF) by up to 5-11 percent/mmHg in normal adults. Here we describe two approaches to generating the CO(2) challenge using a computer-controlled gas blender to administer: i) a square wave change in CO(2) and, ii) a ramp stimulus, consisting of a continuously graded change in CO(2) over a range. Responses were assessed regionally by blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI). Methodology/principal findings We studied 8 patients with known cerebrovascular disease (carotid stenosis or occlusion) and 2 healthy subjects. The square wave stimulus was used to study the dynamics of the vascular response, while the ramp stimulus assessed the steady-state response to CO(2). Cerebrovascular reactivity (CVR) maps were registered by color coding and overlaid on the anatomical scans generated with 3 Tesla MRI to assess the corresponding BOLD signal change/mmHg change in CO(2), voxel-by-voxel. Using a fractal temporal approach, detrended fluctuation analysis (DFA) maps of the processed raw BOLD signal per voxel over the same CO(2) range were generated. Regions of BOLD signal decrease with increased CO(2) (coded blue) were seen in all of these high-risk patients, indicating regions of impaired CVR. All patients also demonstrated regions of altered signal structure on DFA maps (Hurst exponents less than 0.5; coded blue) indicative of anti-persistent noise. While 'blue' CVR maps remained essentially stable over the time of analysis, 'blue' DFA maps improved. Conclusions/significance This combined dual stimulus and dual analysis approach may be complementary in identifying vulnerable brain regions and thus constitute a regional as well as global brain stress test.

Biologically variable ventilation improves lung function in acute respiratory distress models. If enhanced recruitment is responsible for these results, then biologically variable ventilation might promote distribution of exogenous surfactant to nonaerated areas. Our objectives were to confirm model predictions of enhanced recruitment with biologically variable ventilation using computed tomography and to determine whether surfactant replacement with biologically variable ventilation provides additional benefit in a porcine oleic acid injury model.Prospective, randomized, controlled experimental animal investigation.University research laboratory.Domestic pigs.Standardized oleic acid lung injury in pigs randomized to conventional mechanical ventilation or biologically variable ventilation with or without green dye labeled surfactant replacement.Computed tomography-derived total and regional masses and volumes were determined at injury and after 4 hrs of ventilation at the same average low tidal volume and minute ventilation. Hemodynamics, gas exchange, and lung mechanics were determined hourly. Surfactant distribution was determined in postmortem cut lung sections. Biologically variable ventilation alone resulted in 7% recruitment of nonaerated regions (p.03) and 15% recruitment of nonaerated and poorly aerated regions combined (p.04). Total and normally aerated regional volumes increased significantly with biologically variable ventilation, biologically variable ventilation with surfactant replacement, and conventional mechanical ventilation with surfactant replacement, while poorly and nonaerated regions decreased after 4 hrs of ventilation with biologically variable ventilation alone (p.01). Biologically variable ventilation showed the greatest improvement (p.003, biologically variable ventilation vs. all other groups). Hyperaerated regional gas volume increased significantly with biologically variable ventilation, biologically variable ventilation with surfactant replacement, and conventional mechanical ventilation with surfactant replacement. Biologically variable ventilation was associated with restoration of respiratory compliance to preinjury levels and significantly greater improvements in gas exchange at lower peak airway pressures compared to all other groups. Paradoxically, gas exchange and lung mechanics were impaired to a greater extent initially with biologically variable ventilation with surfactant replacement. Peak airway pressure was greater in surfactant-treated animals with either ventilation mode. Surfactant was distributed to the more caudal/injured lung sections with biologically variable ventilation.Quantitative computed tomography analysis confirms lung recruitment with biologically variable ventilation in a porcine oleic acid injury model. Surfactant replacement with biologically variable ventilation provided no additional recruitment benefit and may in fact be harmful.

Background We compared the proportion of ischemic heart disease (IHD) patients newly diagnosed with dementia and depression across three treatment groups: percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) and medical management alone (IHD-medical). Methods and Findings De-identified, individual-level administrative records of health service use for the population of Manitoba, Canada (approximately 1.1 million) were examined. From April 1, 1993 to March 31, 1998, patients were identified with a diagnosis of IHD (ICD-9-CM codes). Index events of CABG or PCI were identified from April 1, 1998 to March 31, 2003. Outcomes were depression or dementia after the index event. Patients were followed forward to March 31, 2006 or until censored. Proportional hazards regression analysis was undertaken. Independent variables examined were age, sex, diabetes, hypertension and income quintile, medical management alone for IHD, or intervention by PCI or CABG. Age, sex, diabetes, and presence of hypertension were all strongly associated with the diagnosis of depression and dementia. There was no association with income quintile. Dementia was less frequent with PCI compared to medical management; (HR = 0.65; p = 0.017). CABG did not provide the same protective effect compared to medical management (HR = 0.90; p = 0.372). New diagnosis depression was more frequent with interventional approaches: PCI (n = 626; hazard ratio = 1.25; p = 0.028) and CABG (n = 1124, HR = 1.32; p = 0.0001) than non-interventional patients (n = 34,508). Subsequent CABG was nearly 16-fold higher (p

Resolution of the acute respiratory distress syndrome (ARDS) requires clearance of pulmonary edema. Biologically variable ventilation (BVV) strategies that improve gas exchange, lung mechanics, and inflammatory mediators in ARDS may be beneficial in this regard. We used quantitative computed tomography (CT), a single indicator thermodilution system (PiCCO®) to determine extravascular lung water (EVLW), and the change in edema protein concentration over time to compare edema clearance with BVV vs conventional mechanical ventilation (CMV) in a porcine ARDS model.Sixteen pigs with oleic acid lung injury were randomized to four hours of ventilation with either CMV (n = 8) or BVV (n = 8) at identical low tidal volume and minute ventilation over time. Hemodynamic variables, gas exchange, lung mechanics, and PiCCO derived EVLW were determined hourly. Computed tomography images and edema fluid samples were obtained at baseline lung injury and after four hours of ventilation. Wet and dry lung weights were determined postmortem.At four hours with BVV, peak airway pressure was decreased significantly and lung compliance improved compared with CMV (P = 0.003; P 0.001, respectively). Hemodynamic variables and gas exchange were not different between groups. Also at four hours, computed tomography revealed an increase in total gas volume (P = 0.001) and a decrease in total lung weight and global lung density (P = 0.005; P = 0.04 respectively) with BVV. These findings were associated with a significant increase in the gas volume of normally aerated lung regions (P 0.001) and a decrease in the poorly and non-aerated lung regions (P = 0.001). No change in any CT parameter occurred with CMV. The lung weights derived from computed tomography correlated well with postmortem wet weights (R(2) = 0.79; P 0.01). The decrease in PiCCO derived EVLW from injury to four hours did not differ significantly between BVV and CMV. Extravascular lung water showed no correlation with postmortem wet weights and significantly underestimated lung water. Average alveolar fluid clearance rates were positive (1.4%·hr(-1) (3%)) with BVV and negative with CMV (-2.0%·hr(-1) (4%)).In a comparison between BVV and CMV, computed tomography evidence suggests that BVV facilitates enhanced clearance and/or redistribution of edema fluid with improved recruitment of atelectatic and poorly aerated lung regions; no such evidence was seen with either single thermodilution measurement of EVLW or edema clearance rates. The results of computed tomography provide further evidence of the benefit of BVV over conventional ventilation in ARDS.

In Canada, research in the field of anesthesiology has been restricted mainly to the domains of basic science and applied physiology. Despite being of valuable scientific relevance and importance, most of this research evaluates physiologic outcomes or surrogate clinical outcomes rather than clinically significant outcomes that could change the way in which we practice. While many medical specialties have appreciated the importance of evaluating outcomes, such as mortality, quality of life, length of stay or efficiency of care, anesthesiology has lagged behind. One of the main reasons Canadian anesthesiology has been slow to embrace outcome studies is the delayed development of a collaborative network of anesthesia investigators to advance multicentre clinical research projects. Clinical research is at a turning point and is rapidly evolving, not only in Canada but worldwide. We strongly believe that Canadian anesthesiologists are capable of markedly improving their research capacity by fostering collaborative outcome-driven research. We further believe that such research can and will change clinical practice. In order to attain this goal, we have initiated a collaborative research network, the Perioperative Anesthesiology Clinical Trials (PACT) group. The PACT group is a collaborative group of Canadian academic anesthesiologists with an interest in the design, implementation, conduct, and publication of multicentre clinical trials in anesthesiology and perioperative medicine. The aim of the PACT initiative is to help anesthesiology clinician investigators 1) to identify and investigate clinically relevant questions in anesthesiology and perioperative medicine; 2) to build research programs that answer their research questions; 3) to structure and conduct quality research with sound methodology; 4) to facilitate collaboration amongst various investigators across Canada so as to conduct multicentre research; 5) to acquire peer-reviewed funding from granting agencies; and finally 6) to execute and publish their results in high-impact peer-reviewed journals. The primary focus of the PACT initiative is to generate knowledge in perioperative anesthesia by providing a forum for the development and implementation of multicentre clinical trials that are designed to answer research questions. It is anticipated that the forum will have a fundamental impact on the practice of anesthesiology and perioperative medicine. In addition, the PACT group will provide mentoring to new investigators as a collaborative network and will facilitate the dissemination of research knowledge, best practices, and standardization of practice parameters, thereby informing the practice of anesthesiology and ensuring its continued advancement as a profession. R. Hall, MD S. Beattie, MD D. Cheng, MD P. Choi, MD A. Y. Denault, MD D. Mazer, MD W. A. C. Mutch, MD A. F. Turgeon, MD H. Yang, MD Perioperative Anesthesiology Clinical Trials Group Steering Committee, Halifax, NS, Canada

Paraplegia remains one of the most devastating complications of thoracoabdominal aortic surgery and is associated with a significant increase in both morbidity and mortality. Modern aortic repair techniques use many modalities aimed at reducing the risk of spinal cord ischemia inherent with surgical management. One of these modalities that acts via optimizing spinal cord blood flow is lumbar cerebrospinal fluid (CSF) drainage. Either alone or in combination with other interventions, CSF drainage remains one of the most frequently used spinal cord protection techniques. Despite no definitive proof of efficacy for reducing spinal cord injury, there are compelling data supporting its use. However, the potential benefit of CSF drainage must be balanced against the risks associated with its use, including nerve injury during insertion, compressive neuraxial hematoma formation, intracranial hemorrhage due to excessive drainage, and infection. The optimal benefit to risk ratio can be achieved by understanding the rationale for its use and following practical management guidelines.

The ability to assess the brain-at-risk during carotid endarterectomy (CEA) under general anesthesia remains a major clinical problem. Point-of-care monitoring can potentially dictate changes to management intraoperatively. In this observational study, we examined the correlation between a series of point-of-care monitors and lactate flux during CEA. Both neurosurgeons and vascular surgeons participated in the study. The patients underwent arterial-jugular venous blood sampling for oxygen, carbon dioxide, glucose, and lactate, n = 26; bispectral index (BIS) monitoring ipsilateral to side of surgery, n = 26; raw and processed electroencephalogram (EEG), n = 22; and bi-frontal cerebral oximetry using the Fore-Sight monitor, n = 20. One patient experienced a new neurological deficit when assessed at 24 hr following surgery. Lactate flux into the brain was correlated with the greatest decrease in cerebral oximetry with carotid cross-clamping; lactate efflux was correlated with the least. The most noticeable changes in processed EEG (density spectral analysis) were also seen with lactate influx, but at a slower time resolution than cerebral oximetry. Loss of autoregulatory behaviour was demonstrated with lactate influx; however, no correlation was seen between lactate flux and BIS monitoring. There was a correlation between cerebral oximetry and lactate flux during carotid cross-clamping. The Fore-Sight monitor may be of value as a point-of-care monitor during CEA under general anesthesia. A novel finding of this study is lactate flux into the brain in the presence of a large difference in cerebral oxygenation during cross-clamping of the carotid artery. Registered at clinicaltrials.gov: NCT000737334.

Mechanical ventilation can be lifesaving for status asthmaticus, but how best to accomplish mechanical ventilation is unclear. Biologically variable ventilation (mechanical ventilation that emulates healthy variation) and conventional control mode ventilation (monotonously regular) were compared in an animal model of bronchospasm to determine which approach yields better gas exchange and respiratory mechanics.A randomized prospective trial of biologically variable ventilation vs. control mode ventilation in swine.University research laboratory.Eighteen farm-raised pigs.Methacholine was administered as a nebulized aerosol to initiate bronchospasm, defined as doubling of peak inspiratory pressure and respiratory system resistance, and then randomized (n = 9 each group) to either continue control mode ventilation or switch to biologically variable ventilation at the same minute ventilation. Over the next 4 hrs, hemodynamics, blood gases, respiratory mechanics, and carbon dioxide expirograms were recorded hourly. At end-experiment, tracheobronchial lavage was undertaken to determine interleukin-6 and -10 concentrations.Measurements of physiologic variables and inflammatory cytokines showed that biologically variable ventilation significantly improved gas exchange, with greater arterial oxygen tensions (p = .006; group x time interaction), lower arterial carbon dioxide tensions (p = .0003; group effect), lower peak inspiratory pressures (p = .0001; group x time), greater static compliance (p = .0001; group x time), greater dynamic compliance (p = .0001; group x time), and lower total respiratory system resistance (p = .028; group x time), compared with conventional ventilation. The appearance of inflammatory cytokines in bronchoalveolar lavage fluid (interleukin-6 and -10) was not affected by mode of ventilation.In this experimental model, biologically variable ventilation was superior to control mode ventilation in terms of gas exchange and respiratory mechanics during severe bronchospasm.