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Importance: Tracheal intubation is one of the most commonly performed and high-risk interventions in critically ill patients. Limited information is available on adverse peri-intubation events. Objective: To evaluate the incidence and nature of adverse peri-intubation events and to assess current practice of intubation in critically ill patients. Design, Setting, and Participants: The International Observational Study to Understand the Impact and Best Practices of Airway Management in Critically Ill Patients (INTUBE) study was an international, multicenter, prospective cohort study involving consecutive critically ill patients undergoing tracheal intubation in the intensive care units (ICUs), emergency departments, and wards, from October 1, 2018, to July 31, 2019 (August 28, 2019, was the final follow-up) in a convenience sample of 197 sites from 29 countries across 5 continents. Exposures: Tracheal intubation. Main Outcomes and Measures: The primary outcome was the incidence of major adverse peri-intubation events defined as at least 1 of the following events occurring within 30 minutes from the start of the intubation procedure: cardiovascular instability (either: systolic pressure 30 minutes, new or increase need of vasopressors or fluid bolus >15 mL/kg), severe hypoxemia (peripheral oxygen saturation

Background The optimal method for blood pressure monitoring in obese surgical patients remains unknown. Arterial catheters can cause potential complications, and noninvasive oscillometry provides only intermittent values. Finger cuff methods allow continuous noninvasive monitoring. The authors tested the hypothesis that the agreement between finger cuff and intraarterial measurements is better than the agreement between oscillometric and intraarterial measurements. Methods This prospective study compared intraarterial (reference method), finger cuff, and oscillometric (upper arm, forearm, and lower leg) blood pressure measurements in 90 obese patients having bariatric surgery using Bland–Altman analysis, four-quadrant plot and concordance analysis (to assess the ability of monitoring methods to follow blood pressure changes), and error grid analysis (to describe the clinical relevance of measurement differences). Results The difference (mean ± SD) between finger cuff and intraarterial measurements was −1 mmHg (± 11 mmHg) for mean arterial pressure, −7 mmHg (± 14 mmHg) for systolic blood pressure, and 0 mmHg (± 11 mmHg) for diastolic blood pressure. Concordance between changes in finger cuff and intraarterial measurements was 88% (mean arterial pressure), 85% (systolic blood pressure), and 81% (diastolic blood pressure). In error grid analysis comparing finger cuff and intraarterial measurements, the proportions of measurements in risk zones A to E were 77.1%, 21.6%, 0.9%, 0.4%, and 0.0% for mean arterial pressure, respectively, and 89.5%, 9.8%, 0.2%, 0.4%, and 0.2%, respectively, for systolic blood pressure. For mean arterial pressure and diastolic blood pressure, absolute agreement and trending agreement between finger cuff and intraarterial measurements were better than between oscillometric (at each of the three measurement sites) and intraarterial measurements. Forearm performed better than upper arm and lower leg monitoring with regard to absolute agreement and trending agreement with intraarterial monitoring. Conclusions The agreement between finger cuff and intraarterial measurements was better than the agreement between oscillometric and intraarterial measurements for mean arterial pressure and diastolic blood pressure in obese patients during surgery. Forearm oscillometry exhibits better measurement performance than upper arm or lower leg oscillometry. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Study Objective To evaluate use of a respiratory volume monitor (RVM; ExSpiron, Respiratory Motion, Inc., Waltham, MA, USA) that provides minute ventilation (MV), tidal volume (TV) and respiratory rate (RR) measurements in obese surgical patients, hitherto undescribed. Design Prospective, IRB-approved observational study of RVM parameter accuracy in obese surgical patients, designed to test the ability of the RVM to detect predefined postoperative respiratory depression (PORD) and apneic events (POA) and to correlate STOP-Bang scores with PORD and POA. Setting Pre-, intra-, and post-op patient-care areas, including the post-anesthesia care unit (PACU) in 2 academic centers with bariatric populations. Patients 80 patients (47±12 years), BMI of 43±7 kg/m 2 undergoing elective surgery were enrolled. Interventions Data collected included patient characteristics, STOP-Bang scores and RVM data from immediately preoperatively through PACU completion without effecting standard clinical care. Measurements Low minute ventilation (LMV) was defined as 40% of predicted MV, and PORD was defined as sustained LMV for 5 minutes. Appropriate parametric and non-parametric statistical analyses were performed, P Main Results In 56 patients with complete intraoperative ventilator data, correlation between RVM and ventilator MV measurements was r=0.89 (measurement bias 1.5%, accuracy 11%). Measurement error was 0.13 L/min (95% confidence interval−0.93 L/min - 1.20 L/min). In PACU, 16.3% and 31% of patients had PORD and POA respectively. There were no significant differences in the incidence of PORD and POA in 3 STOP-Bang risk categories (P>.2). Conclusions There was excellent correlation and accuracy between the RVM and ventilator volumes in obese surgical patients. A considerable number of patients exhibited PORD and POA in the PACU. The STOP-Bang risk scores correlated poorly with PORD and POA which suggests that obese surgical patients remain at risk for early post-operative respiratory events irrespective of the STOP-Bang score.

Study Objective. Reliably identifying patients at risk for postoperative respiratory depression (RD) remains an unmet need. We hypothesized that defined low minute ventilation events (LMVe) near the end of the post-anesthesia care unit (PACU) stay identifies patients at RD risk on the general hospital floor (GHF). Design Prospective observational study. Setting Tertiary care, urban academic medical center. PACU and GHF during the first postoperative night. Patients One hundred-and-nineteen adult, ASA I – III patients undergoing elective surgery under general anesthesia completed the study. Interventions Data collection from a non-invasive respiratory volume monitor and the patients' medical record perioperatively through the first postoperative night. Measurements Minute ventilation (MV), tidal volume (TV) and respiratory rate (RR) were measured continuously in the PACU and on the GHF. MV was counted as the percent of individual predicted MV (MVPRED), and RD was defined as ≥1 LMVe/h on the GHF. Based on the number of LMVes within 30 min before PACU discharge, patients were grouped into A, ‘Not-At-Risk’: 0 LMVe and B, ‘At-Risk’: ≥1 LMVes. Unpaired t-test, Mann-Whitney U test, ANOVA, Kruskal-Wallis test, Fisher's exact test, sensitivity and specificity and ROC curve analyses were applied as appropriate. Main results One hundred-and-six (89%) and 13 (11%) patients met Group A and B criteria respectively. The latter had more LMVe/h on the GHF (median 0.81 vs 0, p ≤ 0.001), and their MVPRED was significantly less. Following opioid administration, the LMVe likelihood was 43% in Group B and 5.6% in Group A. As a predictor for RD on the GHF, the number of LMVe in the last 30 min of PACU, had positive and negative predictive values of 61.5% and 90.6%, respectively. Conclusion Minute ventilation assessment in the PACU as described in this study can be useful to identify patients at risk for postoperative respiratory depression.

During magnetic resonance imaging (MRI), children are at risk for body temperature variations. The cold MRI environment that preserves the MRI magnet can cause serious hypothermia. On the other hand, hyperthermia may also develop because of radiofrequency-induced heating of the tissues, particularly in prolonged examinations. Because of a lack of MRI-compatible core temperature probes, temperature assessment is unreliable, and specific absorption rate-related patient heat gain must be calculated to determine the allowable scan duration. We compared an MRI-compatible temperature probe and a modification thereof to a standard esophageal core body temperature probe in children.Children undergoing general anesthesia were recruited, each patient serving as his/her own control. Core body temperature was measured using 3 different devices: (1) a fiberoptic MRI-compatible skin surface temperature probe (MRI-skin) located on the child's skin surface; (2) a fiberoptic MRI-compatible temperature probe modified with a single-use sleeve at the tip (MRI-core), located in the nasopharynx; and (3) a standard temperature monitor (STRD) located in the esophagus or nasopharynx. The Bland-Altman method was used for statistical analysis.We enrolled 60 children aged 7.8 ± 6 years (mean ± SD) weighing 32.4 (±26.4) kg. The estimated difference between the STRD and MRI-core measurements of core temperature was 0.06°C (confidence interval [CI]: -0.02, 0.15), and between the STRD and the MRI-skin 1.19°C (CI: 0.97, 1.41). According to the Bland-Altman analysis, the 95% limits of agreement ranged from -0.9 to 3.4 and from -1.3 to 1.2 between the STRD and the MRI-skin probe and the MRI-core probe, respectively.Our results show good agreement between standard esophageal measurements of core temperature and core temperature measured using a modified MRI-core probe during general anesthesia in a general surgical pediatric population. The ability to accurately assess core temperature in the MRI suite may safely allow longer scan times and therefore reduce repeat anesthetic exposure, improve patient safety, and enhance the quality of care in children.

Biphalin is an opioid peptide analogue that currently is under clinical development as a new type of site-directed analgesic. In rats, the intrathecal (i.t.) analgesic potency of biphalin is 1000-fold greater than morphine. Such a high activity may reflect this compound's activation of three types of opioid receptors (mu, delta and kappa). NMDA receptors also play an important role in nociceptive processing. Therefore, we investigated in rats whether an NMDA antagonist may influence biphalin-induced antinociception. In the present study, ketamine was chosen because of the widespread safe use of this drug in clinical practice. I.t. application of ketamine alone had relatively little analgesic effect and its excitatory effects limited possible doses of the drug. Co-administration of ketamine with biphalin or morphine produced markedly greater antinociception than biphalin or morphine alone in acute, thermal tail flick testing. These results suggest that NMDA antagonists may be useful potentiators of biphalin analgesia. Thus, to obtain the same spinal antinociceptive effect, lower doses of biphalin or morphine are required when ketamine is co-administered.

To determine separately the effect of corticotropin-releasing hormone (CRH) on analgesia and on inflammation, rats were assigned to receive CRH 60 microg/kg, CRH 300 microg/kg, morphine 4 mg/kg, or normal saline intravenously 15 min before a burn injury. Two mesh chambers that allowed collection of fluid had been previously implanted subdermally in each rat. The skin overlying the right chamber was subject to thermal injury. The left chamber served as a control. We assessed systemic analgesia, and levels of beta-endorphin and corticosterone in plasma and in chamber fluid before, 1, 4 and 24 h after drug administration. The CRH groups exhibited longer tail flick latencies than the control group (P=0.0001) although the increase in latency was of smaller magnitude than in the morphine group. We did not observe a CRH dose response for analgesia. Plasma corticosterone levels were higher in the CRH 300 microg/kg group than in the normal saline group at 4 h (P=0.03). Levels of beta-endorphin in plasma as well as the levels of corticosterone and beta-endorphin in chambers were similar in the CRH 300 microg/kg group and in the normal saline group (all P values0.1). Thus, systemically administered CRH produces analgesia in thermal injury independent of its effect on these two markers of local or systemic inflammation.

The use of “multimodal” combination analgesic therapies or novel single molecules possessing multiple analgesic targets is becoming increasingly attractive. In previous experiments we showed that a substance P antagonist injected intrathecally potentiated the antinociceptive effects of potent opioid receptor agonist, biphalin. Based on examination of the biphalin structure–activity relationship, we designed and synthesized a novel chimeric peptide, termed AA501 (N′(Tyr-D-Ala-Gly-Phe), Nʺ(Z-Trp) hydrazide, Z=benzyloxycarbonyl). AA501 consists of an opioid receptor agonist pharmacophore related to biphalin and a substance P receptor antagonist pharmacophore, both linked by a hydrazide bridge. The present study evaluates the ability of a novel chimeric peptide, AA501, to bind to opioid and substance P receptors and to produce antinociception in tail-flick and formalin tests, and in a neuropathic pain model when administered intrathecally to rats.

Living liver donors for adult liver transplant recipients undergo extensive liver resection. Partial donor hepatectomies may alter postoperative drug metabolism and hemostasis; thus, the risks and the benefits of pain management for this unique patient population may need to be reassessed. The safety and efficacy of combined epidural analgesia and field infiltration in our initial living liver donor group are presented. A thoracic epidural catheter was placed before general anesthesia in 2 female and 6 male donors (44.2 +/- 11.3 years old, mean +/- standard deviation [SD], range 26-56). At the end of surgery, incisions were infiltrated (bupivacaine 0.25%), and an epidural infusion was used (bupivacaine 0.1% + hydromorphone hydrochloride 0.02%). Clinical outcomes were followed for 5 days. The time sequence of pain intensity on a 0-10 visual analog scale clustered into 3 phases, the intensity of which differed significantly from each other (2.2 +/- 0.6, 0.69 +/- 0.2, and 2.37 +/- 0.3 respectively, P = 0.028). Right shoulder pain was observed in 75% of the donors. Sedation, pruritus, and nausea were minimal. Consistently maximal international normalized ratio elevation occurred at 17.6 +/- 7 hours postoperatively, then slowly declined. Platelet counts were lowest on day 3. No neurologic injury or local anesthetic toxicity was observed. This 2-site approach provided effective, safe, postoperative analgesia for our donors. Universally, coagulopathy ensued, indicating a potentially increased risk for epidural hemorrhage at epidural catheter removal and mandating close postoperative neurologic and laboratory monitoring. Research is needed to advance the understanding of postoperative coagulopathy and hepatic dysfunction in these donors to further optimize their perioperative management, including that of analgesia.

SummaryBackground A test dose is used to detect intravascular injection during neuraxial block in pediatrics. Accidental intravascular epidural local anesthetic injection might be unrecognized in anesthetized children leading to potential life-threatening complications. In children, sevoflurane anesthesia blunts the hemodynamic response when intravascular cathecolamines are administered. No studies have explored the hemodynamics and the criteria for a positive test dose result following phenylephrine in sevoflurane anesthetized children. Methods Healthy children undergoing minor procedures were randomly assigned to receive intravenous placebo, or 5 μg∙kg−1 phenylephrine (n = 11/group) during sevoflurane anesthesia. Hemodynamic response was assessed using electrocardiography, pulse oxymetry and non-invasive blood pressure monitoring for 5 min following drug administration in anesthetized patients. Results All patients receiving phenylephrine showed a decreased heart rate (HR) but not all of them met the positive criterion for test dose response. Overall, at 1 min, patients receiving phenylephrine showed a 25% decrease in HR from the baseline while an increase in blood pressure was noticed in 54% of patients receiving phenylephrine. Discussion Phenylephrine might be a future indicator of positive intravascular test dose. Further investigation is needed to find out the phenylephrine dose that elicits a reliable hemodynamic response and whether phenylephrine needs to be dose age-adjusted in order to appreciate relevant hemodynamic changes in children receiving neuraxial blocks undergoing general anesthesia.

Titration of volatile anesthetics to anesthetic effect monitoring using the bispectral index (BIS) has been shown to decrease anesthetic requirements and facilitate recovery from anesthesia unrelated to liver transplantation (OLT). To determine whether availability of such monitoring influences its utilization pattern and affect anesthetic care and outcomes in OLT, we conducted a retrospective analysis in recipients with and without such monitoring. We evaluated annual BIS utilization over a period of 7 years, and compared 41 BIS-monitored patients to 42 controls. All received an isoflurane/air/oxygen and opioid-based anesthetic with planned postoperative ventilation. Data collection included age, body mass index (BMI), gender, Model for End-stage Liver Disease (MELD) score, and time to extubation (TtE). Mean preanhepatic, anhepatic, and postanhepatic end-tidal isoflurane concentrations were compared, as well as BIS values for each phase of OLT using the Kruskal-Wallis and Wilcoxon signed-rank tests, respectively. The use of anesthetic effect monitoring when available increased steadily from 15% of cases in the first year to almost 93% by year 7. There was no significant difference in age, gender, BMI, MELD, or TtE between groups. The BIS group received less inhalational anesthetic during each phase of OLT compared to the control group. However, this difference was statistically significant only during the anhepatic phase (P = .026), and was clinically not impressive. Within the BIS group, the mean BIS value was 38.74 ± 5.25 (mean ± standard deviation), and there was no difference for the BIS value between different transplant phases. Availability of anesthetic effect monitoring as an optional monitoring tool during OLT results in its increasing utilization by anesthesia care teams over time. However, unless integrated into an intraoperative algorithm and an early extubation protocol for fast tracking of OLT recipients, this utilization does not appear to provide a clinical benefit but instead drives cost.

Changes in donor plasma albumin (Alb) and bilirubin (Tbili) are common following right hepatectomy for liver transplantation. We conducted a retrospective study to determine whether the size of the liver resection and the estimated blood loss (EBL) impact these laboratory values in the first week (early) and third week (late) postoperatively.Demographics and peri-operative data of 34 donors undergoing right hepatectomy were analysed by Spearman's correlation (data in means+/-SD, P0.05=statistically significant). Re-admissions for pleural effusions were tracked.Donors were 26-56 (43.3+/-9.1) years old, body mass index (kg/m(2)) was 27.7+/-4.2, liver resected (%) was 58+/-7 and EBL (mL) was 1505+/-927. A larger hepatectomy correlated with lower Alb at 3 weeks (P=0.03) and also with a higher early (P=0.025) and late Tbili (P=0.037). Larger blood loss determined low Alb in the first week (P=0.013), still noticeable 3 weeks postoperatively (P=0.047). Re-admissions for pleural effusion were not associated with the size of the liver resection or postoperative Alb changes.A remaining liver size-dependent reduced synthetic hepatic function may explain the persistent low Alb that becomes apparent at end of the preoperative Albs half-life. A size-related diminished metabolic liver capacity results in early and late elevated Tbili. Prospective studies are needed to better understand the impact of resection size on hepatic physiology, donor care and clinical outcomes.

The opioid peptide dimmer biphalin [(Tyr-D-Ala-Gly-Phe-NH-)(2)] has high potency both in vivo and in vitro. Its antinociceptive activity depends on the route of administration: the lowest potency is after subcutaneous, and the highest after intrathecal or inracerebroventricular administration. We tested the analgesic activity of biphalin in a wide range of doses after intrathecal administration to rats. Doses as low as 0.005 nmol produced significant analgesia. Increasing the dose up to 2 nmol elevated and prolonged antinociception without any evident side effects, indicating that biphalin is an extremely potent opioid after intrathecal application with a wide therapeutic window. The highest dose tested (20 nmol) produced full analgesia and body rigidity lasting 2-3 h. After muscle tone returned to normal, antinociception lasted for several more hours. During these studies we observed a correlation between responses to biphalin and catheter placement. Postmortem verification of catheter placement revealed that in those rats in which high-dose biphalin did not produce analgesia or muscle rigidity, the catheter was positioned incorrectly or the flow of drug solution was obstructed. Therefore, a secondary conclusion is that assessment of transient rigidity after administration of a high dose of biphalin may be used as an easy method to confirm intrathecal placement of the catheter.

We aimed to evaluate the antihyperalgesic efficacy of a combination of hydromorphone (HM) and bupivacaine (BP) delivered via controlled release from a biodegradable cylindrical rod. In vivo studies were performed using a rat model of thermal hyperalgesia induced by chronic constriction injury (CCI) of the sciatic nerve with loose ligatures. Poly(lactic-co-glycolic acid) (PLGA) rods (10 mm length, 1 mm diameter) loaded with HM (5 mg per rod), BP (5 mg per rod) or no drug (placebo) were implanted subcutaneously, in single or dual pairs, adjacent to the constriction injury, immediately after nerve ligation. We evaluated the efficacy of two dose levels for each drug, alone or in combination, in attenuating thermal hyperesthesia over a period of 12 days according to a prevention protocol. Plasma levels of drugs released from the rods and also released in an in vitro simulation were evaluated. In vitro studies demonstrated that drug release is maintained for at least 10 days. HM (5 mg) alone and BP (5 mg) alone did not attenuate hyperalgesia. Their combination provided a significant increase in the paw withdrawal latency as compared to single agents or placebo. When the dose in each group was doubled, implanting four rods, significant attenuation of hyperalgesia was observed. Analyses of rods retrieved after termination of experiments (after 12 days) revealed 30% residual HM and 70% residual BP content. Prolonged delivery of HM and BP alone or in combination via locally applied PLGA rods may offer a feasible alternative to provide long-lasting analgesia.