Pupillary unrest, opioid intensity, and the impact of environmental stimulation on respiratory depression.

Opioid-induced respiratory depression (OIRD) confers significant morbidity, but its onset can be challenging to recognize. Pain or stimulation effects of conversation may mask or attenuate common clinical manifestations of OIRD. We asked whether pupillary unrest could provide an objective signal of opioid exposure, and whether this signal would be independent from the confounding influence of extrinsic stimulation. We conducted a cross-over trial of healthy volunteers using identical remifentanil infusions separated by a washout period; in both, pupillary unrest in ambient light (PUAL) was measured at 2.5-min intervals. During one infusion, investigators continuously engaged the subject in conversation, while in the other, a quiet environment was maintained; measures of respiratory depression were compared under each condition. We tested PUAL's relationship to estimated opioid concentration under quiet conditions, measured PUAL's discrimination of lower versus higher opioid exposure using receiver operating characteristic (ROC) analysis, and assessed the effect of stimulation on PUAL versus opioid using mixed effects regression. Respiratory depression occurred more frequently under quiet conditions (p < 0.0001). Under both conditions, PUAL declined significantly over the course of the remifentanil infusion and rose during recovery (p < 0.0001). PUAL showed excellent discrimination in distinguishing higher versus absent-moderate opioid exposure (AUROC = 0.957 [0.929 to 0.985]), but was unaffected by interactive versus quiet conditions (mean difference, interactive - quiet = - 0.007, 95% CI - 0.016 to 0.002). PUAL is a consistent indicator of opioid effect, and distinguishes higher opioid concentrations independently of the stimulating effects of conversational interaction. Under equivalent opioid exposure, conversational interaction delayed the onset and minimized the severity of OIRD.Clinical trial registration: NCT04301895.

Detection of opioid effect with pupillometry.

BACKGROUND: Opioids produce pupillary constriction but their impact on pupillary unrest and the dynamic parameters of the pupillary light reflex have not been characterized. Given the increasing use of portable pupillometers for care of critically ill patients, it is important to distinguish between opioid effects on the pupil versus those that have been reported to arise from traumatic and ischemic brain insults. We undertook this study to determine which pupillary responses are most profoundly and consistently affected by a progressive infusion of remifentanil. METHODS: We studied the effect of remifentanil on the pupil using two portable infrared pupillometers in 18 volunteers. One pupillometer measured pupillary unrest in ambient light (PUAL) and the other pupillometer measured neurological pupillary index (NPi), constriction velocity (CV), pupil diameter (PD), latency, and % reflex (% reflex) following a transient light flash. Remifentanil was administered at predetermined weight-adjusted rates to raise opioid effect site concentration up to a range known to produce respiratory depression and oxyhemoglobin desaturation, based on a previously published pharmacokinetic model. RESULTS: PUAL was ablated by remifentanil, declining 94 ± 6% from baseline at the time of maximum drug effect. Other pupillary measurements decreased 50-65% from baseline. NPi was unchanged. At the time of oxyhemoglobin desaturation, deviations in PD, CV, and % reflex were widely scattered, whereas PUAL consistently approached zero. CONCLUSION: PUAL is a highly specific indicator of central opioid effect. As a non-invasive measure, it may provide useful data to clinicians who prescribe opioids.

Evaluation of two portable pupillometers to assess clinical utility.

BACKGROUND: Pupillometers have been proposed as clinical assessment tools. We compared two pupillometers to assess measurement agreement. MATERIALS & METHODS: We enrolled 30 subjects and simultaneously measured the pupil diameter and light reflex amplitude with an iPhone pupillometer and a portable infrared pupillometer. We then enrolled 40 additional subjects and made serial measurements with each device. RESULTS: Failure occurred in 30% of attempts made with the iPhone pupillometer compared with 4% of attempts made with the infrared pupillometer (Fisher's exact p = 0.0001). Method comparison of the two devices used simultaneously showed significant disagreement in dynamic measurements. CONCLUSION: The iPhone pupillometer had poor repeatability and suggests that it is not a practical tool to support clinical decisions.

Intraoperative lidocaine infusion and 24-hour postoperative opioid consumption in obese patients undergoing laparoscopic bariatric surgery.

BACKGROUND: Bariatric surgery is the most effective long-term treatment for obesity. Opioid-sparing anesthesia and multimodal analgesia such as lidocaine infusion have been recommended in these patients to reduce opioid-related complications. However, evidence supporting its use for bariatric surgery population is limited. OBJECTIVE: To investigate whether intraoperative lidocaine infusion is associated with decreasing opioid consumption in laparoscopic bariatric surgery. SETTING: A university hospital, California, USA. METHODS: In this retrospective cohort study, outcomes among consecutive obese patients undergoing laparoscopic bariatric surgery between January 2016 to December 2018 were evaluated to determine the impact of adjunctive intraoperative lidocaine infusion on 24-hour postoperative opioid consumption. Secondary outcomes, including opioid consumption during hospitalization, length of stay, and postoperative complications were determined. Post hoc analyses were performed exploring possible dose effects and drug-drug interactions. Univariable and multivariable analyses were performed to identify factors associated with opioid consumption. RESULTS: Among 345 patients, 54 (15.7%) received intraoperative lidocaine infusion (L+) whereas 291 (84.3%) did not receive intraoperative lidocaine infusion (L-). Both L+ and L- groups shared similar demographic characteristics. The 24-hour postoperative opioid consumption was 17.6% lower in L+ (95% confidence interval -28.4 to -5.2, P = .007), but nonsignificantly lower in the multivariate model (12.8%, 95% confidence interval -24.4 to .5, P = .06). Opioid consumption during hospitalization, length of stay, and other clinically significant outcomes did not differ. However, subgroup analysis restricted to opioid-naïve patients indicated significantly reduced opioid consumption in the L+ group. Post hoc analysis suggested interaction between lidocaine and ketamine in decreasing 24-hour postoperative opioid consumption. CONCLUSIONS: Intraoperative lidocaine infusion was not significantly associated with decreasing 24-hour postoperative opioid consumption in obese patients undergoing laparoscopic bariatric surgery.

Pupillary Unrest in Ambient Light and Prediction of Opioid Responsiveness: Case Report on Its Utility in the Management of 2 Patients With Challenging Acute Pain Conditions.

Pupillary unrest in ambient light (PUAL), the normal pattern of pupil diameter fluctuation present in awake humans, has been proposed as a marker of central opioid effect. We report 2 cases in which PUAL identified the appropriate pain management for 2 patients, each with unique, challenging acute pain conditions. In both cases, PUAL accurately predicted opioid responsiveness, suggesting an effective, individualized analgesic approach for both patients.

The Effect of Anesthetic Choice (Sevoflurane Versus Desflurane) and Neuromuscular Management on Speed of Airway Reflex Recovery.

BACKGROUND: Nonintubated patients receiving sevoflurane have slower protective airway reflex recovery after anesthesia compared with patients receiving desflurane. We asked whether this difference would remain significant among intubated patients receiving rocuronium or whether the impact of variable neuromuscular recovery would predominate and thus minimize differences between anesthetics. METHODS: After obtaining written informed consent, patients were randomly assigned to receive sevoflurane (n = 41) or desflurane (n = 40), with neuromuscular monitoring by quantitative train-of-four (TOF) method using accelerometry. Intubation was facilitated by administration of 1 mg/kg rocuronium. Neuromuscular block was produced, with the goal of maintaining 10% to 15% of baseline function. After surgery, neostigmine 70 µg/kg + glycopyrrolate 14 µg/kg was administered. When TOF ratio reached ≥ 0.7, anesthetic was discontinued and fresh gas flow was raised to 15 L/m. The time of first response to command was noted, after which patients were given a 20-mL water swallowing test at 2, 6, 14, 22, 30, and 60 minutes. The following average time intervals were compared between the 2 intervention groups: anesthetic discontinuation to first response to command (T1); first response to command to first successful passing of swallow test (T2); and anesthetic discontinuation to first successful passing of swallow test (T3). We also compared the rates of successful swallow tests at 2 minutes after first response to command in the 2 groups, first categorizing as failures all those who were unable to take the test at 2 minutes, and then excluding 10 patients unable to take the test at this time for reasons other than somnolence (n = 10). RESULTS: Patients receiving desflurane passed the swallowing test at shorter time intervals after first response to command than did patients receiving sevoflurane (Wilcoxon-Mann-Whitney odds = 1.60; 95% confidence interval [CI], 1.01-2.69; P = 0.054). Two minutes after the first response to command, among all 81 patients, the chance of passing the swallowing test was higher after desflurane compared with sevoflurane anesthesia (relative risk = 1.6; 95% CI, 1.0-2.5; P = 0.04). Of the 71 patients (as above), we observed a significantly higher chance of passing at 2 minutes after first response to command (relative risk = 1.8; 95% CI, 1.2-2.7; P = 0.006) in patients receiving desflurane (25/33) compared with those receiving sevoflurane (16/38). In 18 of 81 and 16 of 71 patients, the neuromuscular monitoring and reversal protocols were not followed (neostigmine underdosed, extubation at TOF <0.7, or reliance on tactile as opposed to quantitative TOF measurement). In both the total cohort and the subset of 71, neuromuscular protocol adherence increased the chance of passing the swallow test, independent of anesthetic assignment in multivariable logistic regression (P = 0.02 and P = 0.006, respectively), demonstrating significant effect on airway reflex recovery independent of chosen anesthetic. CONCLUSIONS: Compared with sevoflurane, desflurane allowed faster recovery of airway reflexes after anesthesia in intubated patients. Clinical management of neuromuscular block, including full reversal and the use of quantitative TOF, affects airway reflex recovery-an effect that may be at least as profound as the choice of potent inhaled anesthetic.

Case report: epidural hematoma nine days after removal of a labor epidural catheter.

Timely recognition and surgical decompression are crucial to minimize risk of permanent neurologic deficit from epidural hematoma. We present the case of a patient who developed acute back pain, sensory deficit, and ascending weakness 9 days after removal of a labor epidural catheter. Magnetic resonance imaging revealed a heterogeneous fluid collection extending from C6-7 through the lumbar region, with cord deformity at T9-11. Decompression laminectomy was performed within 4 hours of symptom onset. Twelve hours later, her motor function had fully recovered. Subsequent anatomic and hematologic workup was inconclusive. This presentation is atypical given the delayed presentation of symptoms after epidural placement.

Predictive value of abdominal obesity vs. body mass index for determining risk of intensive care unit mortality.

OBJECTIVE: To explore whether sagittal abdominal diameter as a marker of abdominal obesity is a risk factor for death and morbidity in patients in the intensive care unit and a better outcome determinant for obese patients than body mass index. DESIGN: Prospective, observational study from April 2008 to January 2009. SETTING: Two general intensive care units, both in Toulouse University Hospitals, France. PARTICIPANTS: All adult patients admitted in the two intensive care units except those routinely discharged within 48 hrs or those having conditions with possible effect on anthropometric indices. INTERVENTIONS: Measurement of the sagittal abdominal diameter at admission allowed us to divide the studied population into abdominally obese, underweight, and control groups. MEASUREMENTS AND RESULTS: The primary outcome measure was mortality in the intensive care unit until day 60 after admission. Secondary outcomes were morbidity and length of stay in the intensive care unit. Among 503 patients admitted, 403 were included. At admission, age, diabetes, dyslipidemia, hypertension, Simplified Acute Physiology Score II, and McCabe scores were higher in the abdominally obese group (n = 109) than in the control group (n = 277). The rate of death was higher in the abdominally obese group compared to control (44% vs. 25.3%; p < .01). After adjustment for age, simplified acute physiology score, II and McCabe score, a multivariate analysis showed an increased risk of death in the abdominally obese group (adjusted odds ratio, 2.12; 95% confidence interval, 1.25-3.60). A body mass index >30 kg/m2 was not an independent risk factor for death. During the stay in the intensive care unit, incidence of acute renal failure and abdominal compartment syndrome were higher in the abdominally obese group. CONCLUSION: A high sagittal abdominal diameter, and not a high body mass index, is an independent risk factor of death in critically ill patients.

Airway responses during desflurane versus sevoflurane administration via a laryngeal mask airway in smokers.

Cigarette smokers have a greater risk of respiratory complications during anesthesia compared with nonsmokers. It is not known whether the relative pungency of an inhaled anesthetic further contributes to the smokers' increased rate of such complications. In the present study, we tested whether the use of a more pungent anesthetic (desflurane) would result in a higher rate of coughing, breath holding, laryngospasm, or desaturation among patients who smoke. We randomly assigned 110 smokers to anesthesia with desflurane (n = 55) or sevoflurane (n = 55), administered via a laryngeal mask airway. Five patients (9%) receiving desflurane and nine patients (16%) receiving sevoflurane coughed (P = 0.39). Most coughing occurred during induction (33%) or emergence (56%), in the setting of airway manipulation and low anesthetic concentration. The rate of breath holding, laryngospasm, and desaturation was similar between those receiving desflurane versus sevoflurane. A retrospective comparison of this cohort of 110 smokers to a previous group consisting of 100 nonsmokers and 27 smokers receiving an identical anesthetic regimen indicates that cigarette smoking, but not choice of anesthetic, places patients at increased risk of respiratory complications.

Airway reflexes return more rapidly after desflurane anesthesia than after sevoflurane anesthesia.

Patients given a more soluble inhaled anesthetic usually take longer to awaken from anesthesia than do patients given a less soluble anesthetic. In the present study, we tested whether such a delay in awakening was also associated with a delay in restoration of protective airway reflexes. Patients were randomly assigned to receive desflurane (n = 31) or sevoflurane (n = 33) via a laryngeal mask airway. Demographics did not differ between groups. The average minimum alveolar anesthetic concentration fraction for both groups was 0.62, and the mean (+/-sd) minimum alveolar anesthetic concentration hours was 1.00 +/- 0.68 for desflurane versus 0.95 +/- 0.57 for sevoflurane, although more patients given sevoflurane also received regional anesthesia (17 for sevoflurane and 8 for desflurane). The time from stopping anesthetic administration to appropriate response to command was longer after sevoflurane (5.5 +/- 3.1 versus 3.4 +/- 1.9 min; P < 0.01). In addition, the time from first response to command to ability to swallow 20 mL of water without coughing or drooling was longer after sevoflurane. At 2 min after responding to command, all patients given desflurane were able to swallow without coughing or drooling, whereas 55% of patients given sevoflurane coughed and/or drooled (P < 0.001). At 6 min after responding to command, 18% of patients given sevoflurane still could not swallow without coughing or drooling (P < 0.05). We conclude that desflurane allows an earlier return of protective airway reflexes.

Airway difficulty after a brachial plexus subclavian perivascular block.

IMPLICATIONS: We report a case of upper airway obstruction after subclavian perivascular block in a patient with a preexisting unrecognized paralyzed vocal cord on the opposite side. We discuss the incidence of vocal cord paralysis after subclavian perivascular block and the risk of airway compromise if contralateral vocal cord paralysis is known or suspected.