Increase In End-tidal CO2 Research Articles

Assessing cerebrovascular reactivity (CVR) in rhesus macaques (Macaca mulatta) using a hypercapnic challenge and pseudo-continuous arterial spin labeling (pCASL)

Cerebrovascular reactivity (CVR) is a measure of cerebral small vessels’ ability to respond to changes in metabolic demand and can be quantified using magnetic resonance imaging (MRI) coupled with a vasoactive stimulus. Reduced CVR occurs with neurodegeneration and is associated with cognitive decline. While commonly measured in humans, few studies have evaluated CVR in animal models. Herein, we describe methods to induce hypercapnia in rhesus macaques (Macaca mulatta) under gas anesthesia to measure cerebral blood flow (CBF) and CVR using pseudo-continuous arterial spin labeling (pCASL). Fifteen (13 M, 2 F) adult rhesus macaques underwent pCASL imaging that included a baseline segment (100% O2) followed by a hypercapnic challenge (isoflurane anesthesia with 5% CO2, 95% O2 mixed gas). Relative hypercapnia was defined as an end-tidal CO2 (ETCO2) ≥5 mmHg above baseline ETCO2. The mean ETCO2 during the baseline segment of the pCASL sequence was 34 mmHg (range: 23–48 mmHg). During this segment, mean whole-brain CBF was 51.48 ml/100g/min (range: 21.47–77.23 ml/100g/min). Significant increases (p<0.0001) in ETCO2 were seen upon inspiration of the mixed gas (5% CO2, 95% O2). The mean increase in ETCO2 was 8.5 mmHg and corresponded with a mean increase in CBF of 37.1% (p<0.0001). The mean CVR measured was 4.3%/mmHg. No anesthetic complications occurred as a result of the CO2 challenge. Our methods were effective at inducing a state of relative hypercapnia that corresponds with a detectable increase in whole brain CBF using pCASL MRI. Using these methods, a CO2 challenge can be performed in conjunction with pCASL imaging to evaluate CBF and CVR in rhesus macaques. The measured CVR in rhesus macaques is comparable to human CVR highlighting the translational utility of rhesus macaques in neuroscience research. These methods present a feasible means to measure CVR in comparative models of neurodegeneration and cerebrovascular dysfunction.

End-tidal carbon dioxide after sodium bicarbonate infusion during mechanical ventilation or ongoing cardiopulmonary resuscitation

PurposeEnd-tidal CO2 is used to monitor the ventilation status or hemodynamic efficacy during mechanical ventilation or cardiopulmonary resuscitation (CPR), and it may be affected by various factors including sodium bicarbonate administration. This study investigated changes in end-tidal CO2 after sodium bicarbonate administration. Materials and methodsThis single-center, prospective observational study included adult patients who received sodium bicarbonate during mechanical ventilation or CPR. End-tidal CO2 elevation was defined as an increase of ≥20% from the baseline end-tidal CO2 value. The time to initial increase (lag time, Tlag), time to peak (Tpeak), and duration of the end-tidal CO2 rise (Tduration) were compared between the patients with spontaneous circulation (SC group) and those with ongoing resuscitation (CPR group). ResultsThirty-three patients, (SC group, n = 25; CPR group, n = 8), were included. Compared with the baseline value, the median values of peak end-tidal CO2 after sodium bicarbonate injection increased by 100% (from 21 to 41 mmHg) in all patients, 89.5% (from 21 to 39 mmHg) in the SC group, and 160.2% (from 15 to 41 mmHg) in the CPR group. The median Tlag was 17 s (IQR: 12–21) and the median Tpeak was 35 s (IQR: 27–52). The median Tduration was 420 s (IQR: 90–639). The median Tlag, Tpeak, and Tduration were not significantly different between the groups. Tduration was associated with the amount of sodium bicarbonate for SC group (correlation coefficient: 0.531, p = 0.006). ConclusionThe administration of sodium bicarbonate may lead to a substantial increase in end-tidal CO2 for several minutes in patients with spontaneous circulation and in patients with ongoing CPR. After intravenous administration of sodium bicarbonate, the use of end-tidal CO2 pressure as a physiological indicator may be limited.

Malignant Hyperthermia: Clinical Management

Malignant hyperthermia is a subclinical myopathy in which general anesthesia triggers an uncontrollable contraction of skeletal muscle that leads to a life-threatening hypercatabolic state and an increase in body temperature. The disease is primarily autosomal dominant; mutations in receptors (especially ryanodine receptor type 1) predispose to volatile anesthetic agents or succinylcholine causing an accumulation of intracellular calcium in skeletal muscle that leads to its overactivation and hypermetabolism. In the acute setting, diagnosis is based mainly on clinical presentation and end-tidal capnography, which reveals an increase in end-tidal CO2. Initial treatment measures include discontinuation of the agent causing the reaction and administration of dantrolene. In non-acute settings, there are specific diagnostic tools such as the caffeine-halothane contracture test to confirm suspected cases. MH is a lethal disease and has a high mortality rate if not treated early.

The relationships between age, sex, and cerebrovascular reactivity to hypercapnia using traditional and kinetic-based analyses in healthy adults.

The effect of age and sex on intracranial and extracranial cerebrovascular function is poorly understood. We investigated the relationships between age, sex, and cerebrovascular reactivity (CVR) to hypercapnia in 73 healthy adults (18–80 yr, n = 39 female). CVR to hypercapnia was assessed in the middle cerebral artery (MCA) using transcranial Doppler ultrasound and at the internal carotid artery (ICA) using duplex ultrasound. MCA CVR was characterized by peak MCA velocity (MCAv) response per mmHg increase in end-tidal CO2 and by using a monoexponential model to characterize the kinetics (time constant) of the MCAv response. ICA reactivity was assessed as the relative peak increase in artery diameter. Hierarchical multiple regression determined the relationships between age, sex, and the age-by-sex interaction on all baseline and CVR outcomes. There was no relationship between ICA reactivity (%) with age (P = 0.07), sex (P = 0.56), or a moderator effect of sex on the age effect (P = 0.24). MCAv CVR showed no relationship with age (P = 0.59), sex (P = 0.09), or an age-by-sex moderator effect (P = 0.90). We observed a positive relationship of MCAv CVR time constant with age (P = 0.013), such that the speed of the MCA response was slower with advancing age. The present study provides comprehensive data on age- and sex-specific relationships with intracranial and extracranial cerebrovascular responses to hypercapnia. Despite similar MCAv CVR and ICA reactivity between sexes, kinetic responses of the MCA revealed a slower rate of adjustment with advancing age.NEW & NOTEWORTHY We observed similar MCA CVR and ICA reactivity in males and females. However, kinetic responses of the MCA to hypercapnia suggest that advancing age slows down the rate at which MCA velocity increases in response to hypercapnia. These data indicate distinct regulatory differences, and an impaired vasomotor control of the cerebrovasculature with advancing age, not detected by traditional methods.

Latent Mixture Modeling to Identify Homogeneous Subgroups Predictive of Cerebrovascular Reactivity

IntroductionPrecision medicine is a growing topic of research within the medical community. However, the complex factors that influence disease progression and treatment efficacy often make the identification of small subgroups within large clinical populations challenging. Without strategies to identify subgroups that differentially respond to intervention, researchers and clinicians could overlook treatments that may benefit specific aspects within sizable clinical populations. Cerebrovascular disease results from the interaction of multiple risk factors, leading to varying pathologies including stroke and dementia. Identifying subgroups within the scope of cerebrovascular dysfunction risk will allow researchers to better identify individuals at risk for cerebrovascular disease and ultimately inform optimal treatment strategies. Latent mixture modeling (LMM) presents a novel, unbiased method to identify small homogeneous subgroups that have similar traits within the context of large heterogeneous cohorts. Using LMM, it is possible to detect the presence of latent categorical variables which correspond to unobserved subgroups. To assess the feasibility of LMM as a technique for forming subgroups that predict cerebrovascular health, we retrospectively analyzed data from 78 individuals including 12 measures of physical, metabolic, and cognitive health. Our hypothesis was that latent mixture modeling would identify subgroups formed around similar characteristics of physical, metabolic, cognitive, and psychological health. Further, we hypothesized that these subgroups would display differences in cerebrovascular reactivity (CVR).MethodsData from previous experiments conducted in our laboratory between 2018‐2020 were organized and prepared for analysis. Health measures included: body mass index, systolic blood pressure, heart rate, non‐HDL cholesterol, white blood cell count, albumin/globulin ratio, blood glucose, serum creatinine, total recall memory score, and patient‐reported perception of fear and anxiety. CVR was measured by transcranial Doppler ultrasound and calculated as the percent change (from baseline) in middle cerebral artery blood velocity (MCAv) per mmHg following a forced +9mmHg increase in end‐tidal CO2. LMM was used to identify latent classes based on the selected health measures, and then to assess whether CVR differed among the identified classes. The number of classes was picked based after examining a number of criteria including: Akaike, Bayesian, Sample Size Adjusted Bayesian Information Criteria, Entropy, and the VLMR and adjusted VLMR likelihood ratio tests. The BCH procedure was used for post‐hoc comparisons among classes.ResultsWe identified 4 homogeneous subgroup classes within our data. CVR was found to be significantly different when comparing class 1 and class 2 (p= 0.012) and there was a trend towards significance when comparing class 2 and class 4 (p= 0.063). These data suggest that the interaction of healthspan indicators influence differences in cerebrovascular endothelial function.

Intracranial Cerebrovascular Reactivity by Traditional and Novel Methods in Young, Middle, and Old Aged Healthy Males and Females

ObjectiveLower cerebrovascular reactivity (CVR) to hypercapnia is associated with increased risk of age‐related cognitive decline and all‐cause mortality. Despite the important clinical implications of CVR, evidence of the physiological changes across the healthy adult lifespan is conflicting, with limited findings in females. The aim of this study was to assess the effect of age and sex on CVR. We hypothesized: 1) CVR to be lower in middle‐aged and older compared to young adults, and 2) a higher CVR in young females compared with young males, and a higher CVR in older males than older females.MethodsYoung (n=25, 12 female, age 27±1.5y), middle‐age (n=31, 18 female, age 54±7.3y) and older healthy participants (n=20, 10 female, age 70±2.5y) completed CVR via inhalation of 5% carbon dioxide (CO2) for 5 minutes. Traditional CVR was characterized by the peak middle cerebral artery velocity (MCAv) response per mmHg increase in end‐tidal CO2 (traditional cm/s‐1mmHg), and using a novel mono‐exponential model to characterize the dynamic onset response of the MCAv. Independent samples ANOVA was used to compare main and interaction effects of age and sex.ResultsTraditional CVR was not different between young, middle and older groups (2.0±0.7 vs 1.8±0.9 vs 1.9±0.9 cm/s‐1mmHg; P=0.102). Dynamic onset (novel) responses revealed the time constant of the MCAv response was significantly slower in older and middle‐aged compared to young adults (29±16 vs 27±20 vs 14±9 seconds, P=0.03). No effects of sex were observed for traditional or novel CVR (P≥0.14), but young females had a higher baseline MCAv than young males (70.8 vs 78.6 cm/s‐1P=0.04), which was not observed in middle and older age adults.ConclusionsCVR is preserved in ageing adults, but the speed of the MCAv response is blunted in older and middle‐aged adults compared to young adults. Utilizing dynamic onset responses reveal underlying differences in cerebral regulation with healthy ageing that were not detected by traditional methods.

Physiological responses to cuddling babies with hypoxic–ischaemic encephalopathy during therapeutic hypothermia: an observational study

ObjectivesTo determine whether parents cuddling infants during therapeutic hypothermia (TH) would affect cooling therapy, cardiorespiratory or neurophysiological measures. The secondary aim was to explore parent–infant bonding, maternal postnatal depression and...

Influence of study design on effects of mask wearing on fMRI BOLD contrast and systemic physiology — A comment on Law et al. (2021)

In a study by Law and colleagues recently published in Neuroimage, the authors reported that wearing a surgical mask during an fMRI scan leads to a statistically significant subject-specific change (30%) in the baseline BOLD level in gray matter, although the response to a sensory-motor task was unaffected. An average increase in end-tidal CO2 of 7.4% was found when wearing a mask, despite little support in the literature for major effects of mask wearing on blood gas levels. We comment on these findings, point out a several relevant limitations of the study design and provide alternative interpretations of these data.

Efficacy of Tocilizumab in the treatment of severe COVID-19 patients with respiratory failure

Objective: This study aimed to investigate the impact of tocilizumab, an IL6R inhibitor, on clinical features and laboratory tests of subjects admitted with severe COVID-19 and respiratory failure.&#x0D; Material and Methods: A total of 30 patients with positive polymerase chain reaction for COVID-19 and respiratory failure were analyzed in a retrospective manner. All patients received 8mg/kg body weight tocilizumab i.v. once in addition to the standard COVID-19 treatment protocol, including Oseltamivir phosphate 75mg twice daily, hydroxychloroquine 200 mg twice daily, and azitromycine 250 mg once daily following a 500 mg loading dose. Demographic characteristics, and clinical features including oxygen saturation, the concentration of oxygen inhalation, body temperature, mean arterial pressure and heart rate, and SpO2, end-tidal CO2, and blood tests including complete blood count, procalcitonin, C-reactive protein (CRP), Troponin-I, D-dimer, and liver and kidney function tests were recorded before and after treatment with tocilizumab.&#x0D; Results: A significant increase occurred in SaO2 on first and third days following treatment with tocilizumab (84.3 % and 90.3%, respectively, p&lt;0.001 for both recordings compared to baseline). There was also a significant increase in end-tidal CO2. The increase in mean SaO2 after tocilizumab was followed by a decline in respiratory rate on the first and third days of treatment. A dramatic decline was observed in body temperature from the first day of treatment with tocilizumab. Lymphocyte count increased following tocilizumab and C-reactive protein and Troponin I levels were reduced.&#x0D; Conclusion: Tocilizumab appears as an effective therapeutic option for improving oxygenation, symptoms and laboratory surrogates of ongoing inflammation in subjects with severe COVID-19.

Usefulness of Measurement of End-tidal CO2 Using a Portable Capnometer in Patients with Chronic Respiratory Failure Receiving Long-term Oxygen Therapy.

Objective Patients with chronic respiratory failure requiring long-term oxygen therapy (LTOT) are at a risk of CO2 retention because of excessive oxygen administration. The CapnoEye™ is a novel portable capnometer that can measure end-tidal CO2 (EtCO2) noninvasively. This retrospective study evaluated the usefulness of this device. Methods EtCO2 was measured using the CapnoEye™. The EtCO2 and partial pressure of venous carbon dioxide (PvCO2) were analyzed, and other clinical data were assessed. Patients Sixty-one consecutive patients with chronic respiratory failure receiving LTOT in the outpatient department at the Japanese Red Cross Medical Center between July 2017 and March 2018 were retrospectively reviewed. Results There was a significant correlation between EtCO2 and PvCO2 (r=0.63) in the total study population as well as in the COPD group (r=0.65) and ILD group (r=0.67). The PvCO2 and EtCO2 gradient was correlated with only the body mass index in a multivariate analysis (p=0.0235). The EtCO2 levels on the day of admission were significantly higher than those in the same patients when they were in a stable condition (p=0.0049). There was a significant correlation between ΔEtCO2 and ΔPvCO2 (r=0.4). A receiver-operating characteristic curve analysis revealed the optimal cut-off EtCO2 value for identifying hypercapnia to be 34 mmHg (p=0.0005). Conclusion The evaluation of EtCO2 by the CapnoEye™ was useful for predicting PvCO2. The body mass index was identified as a possible predictor of the PvCO2 and EtCO2 gradient. An increase in EtCO2 may indicate deterioration of the respiratory status in patients with chronic respiratory failure receiving LTOT.

Safety of chronic obstructive pulmonary disease patients undergoing carbon dioxide insufflation in extended endoscopic procedures

Introduction:Carbon dioxide (CO2) insufflation for endoscopies has been shown to be more comfortable and safe, but only in patients without underlying chronic obstructive pulmonary disease (COPD). The aim of this study was to show that using CO2 is safe in COPD patients.Methods:Patients were retrospectively identified who underwent extended endoscopic procedures during the time period of January 2012 to December 2017. Patients were included if they also had COPD. A matched control group without COPD was created during the same timeframe. All the patients were sedated with continuous monitoring of their CO2 levels by end-tidal CO2 (EtCO2).Results:One hundred and ten patients had COPD and underwent an extended endoscopic procedure. These patients had a higher severity of their comorbidities (American Society of Anesthesiologists class 3 or 4) (93.6% [95% confidence interval [CI], 87.4%–96.9%] vs. 60.3% [95% CI, 51.1%–69.0%]; P < 0.01) and an increase of co-existing obstructive sleep apnea (33.6% vs. 6.3%, P < 0.01). There was no difference in baseline EtCO2, but the peak EtCO2 and postprocedure EtCO2 were both significantly higher in the COPD group. The only postprocedural complication found was an inability to be extubated immediately following the procedure with subsequent need to hospitalize the patient, which occurred in three patients (2.8%; 95% CI, 0.9%–7.9%) in the COPD group and one (0.9%; 95% CI, 0.2%–4.9%) in the non-COPD group (P = 0.37).Conclusion:The present study, which was the only study looking at CO2 insufflation specifically in COPD patients, provides evidence that CO2 insufflation is safe in COPD despite a slight increase in EtCO2.

Abstract 28: Feasibility and Safety of Pre-Hospital Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) in Non-Traumatic Out-Of-Hospital Cardiac Arrest

Introduction: The proportion of patients surviving to hospital discharge after out of hospital cardiac arrest (OHCA) is low and any measure that may improve circulation to vital organs during cardiopulmonary resuscitation (CPR) is beneficial. The use of resuscitative endovascular balloon occlusion of the aorta (REBOA) will redistribute cardiac output to the organs proximal to the occlusion. Animal studies supports that aortic occlusion during CPR might benefit patients suffering from OHCA, but human data are scarce. Methods: We performed an observational study at the helicopter emergency medical service in Trondheim (Norway) to assess the feasibility and safety of establishing REBOA in OHCA patients. The femoral artery was identified by ultrasound and a REBOA catheter was placed in the thoracic aorta. All patients received advanced cardiac life support (ACLS) during the procedure. REBOA eligibility, procedural success and time intervals were registered. A safety monitoring program was conducted to ensure that the procedure did not interfere with the quality of ACLS. Results: REBOA was initiated in ten of 98 OHCA patients. The mean age was 63 years (55-71) and 7 were male. The REBOA procedure was successful in all cases (100%), with 80% success rate on first cannulation attempt. Mean REBOA procedural time was 11,7 minutes (8-16, SD 3,2). End-tidal CO2 (EtCO2) increased by a mean of 1.9 kPa at 60 seconds after inflation compared to baseline (p &lt; 0.001). Six of 10 patients (60%) achieved return of spontaneous circulation, 3 (30%) was admitted to hospital. 30-day survival was 10%. The mean width of the femoral artery and vein during CPR was 5,9 mm (3,6 - 7,4, SD 1,2) and 9,4 mm (5,0 - 12,9, SD 2,9), respectively. The safety monitoring group identified no negative influence on the ACLS quality. Conclusions: This is the first study to assess the pre-hospital use of REBOA in patients with non-traumatic cardiac arrest. The REBOA procedure does not interfere with the quality of the ACLS. REBOA is a feasible adjunct treatment in OHCA. The significant increase in EtCO2 after occlusion suggests improved organ circulation during CPR.

Abstract 20: Peripheral Intravenous Analysis Detects Return of Spontaneous Circulation Without Interruption of Chest Compressions in a Rat Model of Cardiopulmonary Resuscitation

Introduction: A higher chest compression fraction (CCF) or percentage of time providing chest compressions is associated with improved survival after cardiac arrest (CA). Pauses in chest compression duration during cardiopulmonary resuscitation (CPR) to palpate a pulse can reduce the CCF. Peripheral Intravenous Analysis (PIVA) is a novel method for determining cardiac and volume status using waveforms from a standard peripheral intravenous (IV) line. We hypothesize that PIVA will demonstrate the onset of return of spontaneous circulation (ROSC) without interruption of CPR. Methods: Eight Zucker Diabetic Fatty (ZDF) rats (4 lean, 4 diabetic) were intubated, ventilated, and cannulated with a 24g IV in the tail vein and a 22g IV in the femoral artery, each connected to a TruWave pressure transducer. Mechanical ventilation was discontinued to achieve CA. After 8 minutes, CPR began with mechanical ventilation, IV epinephrine, and chest compressions using 1.5 cm at 200 times per minute until mean arterial pressure (MAP) increased to 120 mmHg per arterial line. All waveforms were recorded and analyzed in LabChart. PIVA was measured using a Fourier transform of the peripheral venous waveform. Data are mean ± SD. Statistics: Unpaired student’s t-test (two-tailed), α = 05. Results: CA and ROSC were achieved in all 8 rats. Within 1 minute of CPR, there was a 70 ± 35 fold increase/decrease in PIVA during CPR that was temporally associated with ROSC. Within 8 ± 13 seconds of a reduction in PIVA, there was a rapid increase in end-tidal CO 2 . In all rats, ROSC occurred within 38 ± 9 seconds of the maximum PIVA value. Peripheral venous pressure decreased by 1.2 ± 0.9 mmHg during resuscitation and ROSC, which was not significant different at p=0.05. Conclusion: In this pilot study, PIVA detected ROSC without interrupting CPR. Use of PIVA may obviate the need pause CPR for pulse checks, and may result in a higher CCF and survival. Future studies will focus on PIVA and CPR efficacy.

Reduced arterial compliance along the cerebrovascular tree predicts cognitive slowing in multiple sclerosis: Evidence for a neurovascular uncoupling hypothesis

Background: Cognitive slowing occurs in ~70% of multiple sclerosis (MS) patients. The pathophysiology of this slowing is unknown. Neurovascular coupling, acute localized blood flow increases following neural activity, is essential for efficient cognition. Loss of vascular compliance along the cerebrovascular tree would result in suboptimal vasodilation, neurovascular uncoupling, and cognitive slowing. Objective: To assess vascular compliance along the cerebrovascular tree and its relationship to MS-related cognition. Methods: We tested vascular compliance along the cerebrovascular tree by dividing cerebral cortex into nested layers. MS patients and healthy controls were scanned using a dual-echo functional magnetic resonance imaging (fMRI) sequence while they periodically inhaled room air and hypercapnic gas mixture. Cerebrovascular reactivity was calculated from both cerebral blood flow (arterial) and blood-oxygen-level-dependent signal (venous) increases per unit increase in end-tidal CO2. Results: Arterial cerebrovascular reactivity changes along the cerebrovascular tree were reduced in cognitively slow MS compared to cognitively normal MS and healthy controls. These changes were fit to exponential functions, the decay constant (arterial compliance index; ACI) of which was associated with individual subjects’ reaction time and predicted reaction time after controlling for disease processes. Conclusion: Such associations suggest prospects for utility of ACI in predicting future cognitive disturbances, monitoring cognitive deficiencies and therapeutic responses, and implicates neurovascular uncoupling as a mechanism of cognitive slowing in MS.

Regional pulmonary perfusion patterns in humans are not significantly altered by inspiratory hypercapnia.

Pulmonary vascular tone is known to be sensitive to both local alveolar Po2 and Pco2. Although the effects of hypoxia are well studied, the hypercapnic response is relatively less understood. We assessed changes in regional pulmonary blood flow in humans in response to hypercapnia using previously developed MRI techniques. Dynamic measures of blood flow were made in a single slice of the right lung of seven healthy volunteers following a block-stimulus paradigm (baseline, challenge, recovery), with CO2 added to inspired gas during the challenge block to effect a 7-Torr increase in end-tidal CO2. Effects of hypercapnia on blood flow were evaluated based on changes in spatiotemporal variability (fluctuation dispersion, FD) and in regional perfusion patterns in comparison to hypoxic effects previously studied. Hypercapnia increased FD 2.5% from baseline (relative to control), which was not statistically significant (P = 0.07). Regional perfusion patterns were not significantly changed as a result of increased (P = 0.90). Reanalysis of previously collected data using a similar protocol but with the physiological challenge replaced by decreased ( = 0.125) showed marked flow redistribution (P = 0.01) with the suggestion of a gravitational pattern, demonstrating hypoxia has the ability to affect regional change with a global stimulus. Taken together, these data indicate that hypercapnia of this magnitude does not lead to appreciable changes in the distribution of pulmonary perfusion, and that this may represent an interesting distinction between the hypoxic and hypercapnic regulatory response.NEW & NOTEWORTHY Although it is well known that the pulmonary circulation responds to local alveolar hypoxia, and that this mechanism may facilitate ventilation-perfusion matching, the relative role of CO2 is not well appreciated. This study demonstrates that an inspiratory hypercapnic stimulus is significantly less effective at inducing changes in pulmonary perfusion patterns than inspiratory hypoxia, suggesting that in these circumstances hypercapnia is not sufficient to induce substantial integrated feedback control of ventilation-perfusion mismatch across the lung.

Effects of tourniquet usage in lower extremity surgery on optic nerve sheath diameter

Background/aim: The aim of this study was to evaluate changes in intracranial pressure following tourniquet deflation using noninvasive ultrasonographic optic nerve sheath diameter (ONSD) measurements. Materials and methods: Our study included 59 adult patients between the ages of 18 and 65 years from the American Society of Anesthesiologists (ASA) I/II risk groups who were scheduled to undergo elective orthopedic surgery of the lower extremities using a tourniquet under general anesthesia. ONSD and end-tidal CO2 (ETCO2) were measured 5 times: 15 min prior to the anesthesia induction; just prior to the deflation of the tourniquet; and at 5, 10, and 15 min after the deflation. Additionally, age, sex, weight, height, ASA score, and duration of operation and tourniquet usage were recorded. Results: The ONSD value measured 5 min after the deflation was significantly higher than all of the remaining measurements. There was a significant correlation between the ONSD and ETCO2 measurements at 5 and 10 min after deflation (r = 0.61, 95% CI 0.42-0.75, P < 0.0001 and r = 0.30, 95% CI 0.04-0.51, P < 0.05, respectively). Conclusion: The ultrasonographic ONSD measurements, which were obtained using a simple and noninvasive approach, increased significantly following tourniquet deflation, and this increase was correlated with an increase in ETCO2.

Insufflation With Carbon Dioxide During Pediatric Colonoscopy for Control of Postprocedure Pain.

To determine if carbon dioxide (CO2) insufflation in children would improve postprocedure pain following colonoscopy in children. CO2 insufflation during colonoscopy has been found to reduce postcolonoscopy pain in the adult population, but limited data exist in pediatrics. We conducted a prospective study with 40 pediatric patients scheduled for outpatient colonoscopy. Patients were enrolled continuously and were randomized to receive CO2 or air insufflation. Patients and colonoscopists were blinded to insufflation method. End tidal CO2 (EtCO2) was documented throughout the procedure. Abdominal pain was established preprocedure then at 1-, 6-, and 24-hour postprocedure. Subject demographics, indications, colonoscopists' year of training, time to cecum, adverse events, and final diagnoses were recorded. Twenty patients were randomized to each group. Patients receiving air had a statistically significant increase in pain from baseline at 1- and 6-hours after colonoscopy (P=0.007 and 0.008). This was not seen in the CO2 group (P=0.740 and 0.289). There was an increase in postprocedure pain in the air group compared with CO2 group at the 1-hour mark (P=0.032). EtCO2 increased during the procedure, regardless of insufflation method, but no difference was seen between groups (P=0.822). Our results demonstrate that higher levels of pain were reported by patients following air compared with those receiving CO2 insufflation. This is the first study to show CO2 is as safe as air, with no increase in EtCO2 between groups in the pediatric population. CO2 is an effective and safe modality and should be considered for pediatric colonoscopies.

Thoracoscopic Repair of Congenital Diaphragmatic Hernia After Extracorporeal Membrane Oxygenation: Feasibility and Outcomes.

Thoracoscopic repair of congenital diaphragmatic hernia (CDH) has been associated with faster recovery, earlier extubation, and decreased morbidity. Nevertheless, thoracoscopic repair is rarely attempted in the post-extracorporeal membrane oxygenation (ECMO) patient. Commonly cited reasons for not attempting thoracoscopy include concerns that the patients' respiratory status is too tenuous to tolerate insufflation pressures or that presumed defect size is so large that it precludes thoracoscopic repair. Our purpose is to review our experience with post-ECMO thoracoscopic CDH repair and evaluate the success of this approach. We performed retrospective analysis of attempted thoracoscopic CDH repairs after ECMO decannulation at our institution from 2001 to 2015. Primary outcome was rate of conversion. Secondary outcomes were intraoperative end-tidal CO2, time to extubation, and rate of recurrence. We identified 21 post-ECMO patients in whom thoracoscopic CDH repair was attempted. Thoracoscopic repair was successfully completed in 28%. No patients had reported intolerance to insufflation at 3-7 mmHg. Average end-tidal CO2 at 15 operative minutes was 36.9 mmHg in the thoracoscopic group versus 50.7 mmHg in the open group and at 60 minutes was 34.25 mmHg versus 45.6 mmHg, respectively. One patient in the thoracoscopic group died and 1 experienced a large pneumothorax. In the converted group there was one clinically significant pneumothorax and three pleural effusions. Survivors after thoracoscopy were extubated an average of 5.6 ± 2.6 days after surgery versus 19.4 ± 10 days in the converted group (P < .05). Recurrence rates at last follow-up were equal between the two groups at 20%. Thoracoscopic CDH repair is both safe and feasible after ECMO with no increase in operative morbidity or mortality. Insufflation pressures of 3-7 mmHg are well tolerated without undue increase in end-tidal CO2. When compared to conversion cases, thoracoscopic repair is associated with significantly decreased time to extubation with no difference in recurrence.

The Relationship between Cerebral Vasoreactivity and Post-Concussive Symptom Severity.

While pathophysiology underlying post-concussion symptom burden is unknown, data suggest that cerebrovascular dysfunction may be among the culprits. We sought to determine whether the degree of impairment in the ability of cerebrovasculature to buffer against changes in arterial gases (vasoreactivity) is associated with concussion symptoms. In 15 participants (19 ± 5 years, 1 week to 1 year post-injury) diagnosed with concussion, we assessed vasoreactivity from the slope of the linear relationship of beat-by-beat middle cerebral artery blood flow velocity (transcranial Doppler ultrasound) to end-tidal CO2 during progressive increases in end-tidal CO2 (air rebreathing). Symptom burden was assessed using the Post-Concussion Symptom Scale. Subsequently, we explored the relationship between vasoreactivity and the severity of post-concussion headache and cognitive difficulties by linear models. During rebreathing, CO2 increased from 32.6 ± 1.6 to 46.8 ± 1.8 mmHg and cerebrovascular conductance (i.e., flow velocity over pressure) increased from 0.48 ± 0.04 to 0.74 ± 0.06 cms-1 mmHg-1. There was a strong linear relationship between the increase in CO2 and in conductance (R2 = 0.81 ± 0.05; p < 0.05). On average, cerebral vasoreactivity was 0.018 ± 0.003 cm-1 s-1 mmHg CO2-1. Although vasoreactivity tended to be somewhat higher in the asymptotic participants (0.019 ± 0.003 vs. 0.015 ± 0.005 cm-1 s-1 mmHg CO2-1), this difference was not statistically significant (p = 0.48). Higher vasoreactivity was strongly associated with more severe headaches (R2 = 0.57; p < 0.01) and worse cognitive symptoms (R2 = 0.71; p < 0.01). Thus, cerebral vasoreactivity relates strongly to post-concussive headache and cognitive symptom burden. This has significant implications for understanding the pathophysiology underlying post-concussive symptom burden and for devising effective treatment options.

Functional analysis of RYR1 variants linked to malignant hyperthermia

ABSTRACTMalignant hyperthermia manifests as a rapid and sustained rise in temperature in response to pharmacological triggering agents, e.g. inhalational anesthetics and the muscle relaxant suxamethonium. Other clinical signs include an increase in end-tidal CO2, increased O2 consumption, as well as tachycardia, and if untreated a malignant hyperthermia episode can result in death. The metabolic changes are caused by dysregulation of skeletal muscle Ca2+ homeostasis, resulting from a defective ryanodine receptor Ca2+ channel, which resides in the sarcoplasmic reticulum and controls the flux of Ca2+ ions from intracellular stores to the cytoplasm. Most genetic variants associated with susceptibility to malignant hyperthermia occur in the RYR1 gene encoding the ryanodine receptor type 1. While malignant hyperthermia susceptibility can be diagnosed by in vitro contracture testing of skeletal muscle biopsy tissue, it is advantageous to use DNA testing. Currently only 35 of over 400 potential variants in RYR1 have been classed as functionally causative of malignant hyperthermia and thus can be used for DNA diagnostic tests. Here we describe functional analysis of 2 RYR1 variants (c. 7042_7044delCAG, p.ΔGlu2348 and c.641C>T, p.Thr214Met) that occur in the same malignant hyperthermia susceptible family. The p.Glu2348 deletion, causes hypersensitivity to ryanodine receptor agonists using in vitro analysis of cloned human RYR1 cDNA expressed in HEK293T cells, while the Thr214Met substitution, does not appear to significantly alter sensitivity to agonist in the same system. We suggest that the c. 7042_7044delCAG, p.ΔGlu2348 RYR1 variant could be added to the list of diagnostic mutations for susceptibility to malignant hyperthermia.