Remifentanil pharmacodynamics during conscious sedation using algometry: a more clinically relevant pharmacodynamical model.

BACKGROUND: The Minto remifentanil pharmacokinetic/pharmacodynamic (PK/PD) model is used in target-controlled infusion (TCI) devices. The endpoint used to calculate the PD parameters, including the ke0, was the electroencephalogram (EEG), which only changes at high remifentanil concentrations. As the ke0 should adequately predict the time course of drug effects at clinically relevant concentrations, we evaluated the temporal agreement between effect-site concentrations estimated with the Minto model and pressure pain thresholds during conscious sedation. METHODS: We enrolled 100 patients scheduled for gynaecological surgery. The first group (35 subjects) received an effect site targeted remifentanil infusion (target 1.5 ng ml-1); the second group (35 subjects) received the same infusion and a 1 mg bolus of midazolam to evaluate anxiolytic effects; the control group (30 subjects) received a saline infusion. Algometry and vital signs were measured at different time points. RESULTS: The Minto model predicted stable effect-site concentrations within 1.5 min of starting the infusion. Haemodynamic variables stabilised within 5 min, whereas there was a significant increase in pressure pain threshold for up to 15 min in both remifentanil groups. Midazolam had no effect on pressure pain threshold. A PD model based on algometry and Minto PK model was developed. CONCLUSIONS: Our results demonstrate the limitation of the Minto PD model at low target remifentanil concentrations, with a discrepancy in the time course between EEG and pressure pain threshold changes. Clinicians should be aware that the time course of onset of analgesic effects is slower than the estimates of the Minto model. Investigators should consider using algometry data in future opioid PD modelling studies.

Double-lumen endotracheal tubes and bronchial blockers exhibit similar lung collapse physiology during lung isolation.

PURPOSE: Double-lumen endotracheal tubes (DL-ETT) and bronchial blockers (BB) are frequently used to allow one-lung ventilation (OLV) during video-assisted thoracic surgery (VATS). Recently, faster lung collapse has been documented with a BB than with a DL-ETT. The physiologic mechanisms behind this faster collapse remained unknown. We aimed to measure ambient air absorption (Vresorb) and intra-bronchial pressure (Pairway) into the non-ventilated lung during OLV using DL-ETT and BB. METHODS: Patients undergoing VATS and OLV for lung resection were randomly assigned to have measurements made of Vresorb or Pairway within the non-ventilated lung using either a DL-ETT or BB. RESULTS: Thirty-nine patients were included in the analyses. The mean (standard error of the mean [SEM]) Vresorb was similar in the DL-ETT and BB groups [504 (85) vs 630 (86) mL, respectively; mean difference, 126; 95% confidence interval [CI], -128 to 380; P = 0.31]. The mean (SEM) Pairway became progressively negative in the non-ventilated lung in both the DL-ETT and the BB groups reaching [-20 (5) and -31 (10) cmH2O, respectively; mean difference, -11; 95% CI, -34 to 12; P = 0.44] at the time of the pleural opening. CONCLUSIONS: During OLV before pleural opening, entrainment of ambient air into the non-ventilated lung occurs when the lumen of the lung isolation device is kept open. This phenomenon is prevented by occluding the lumen of the isolation device before pleural opening, resulting in a progressive build-up of negative pressure in the non-ventilated lung. Future clinical studies are needed to confirm these physiologic results and their impact on lung collapse and operative outcomes. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT02919267); registered 28 September 2016.

RéSUMé: OBJECTIF: Les tubes endotrachéaux à double lumière (TET-DL) et les bloqueurs bronchiques (BB) sont fréquemment utilisés pour l'isolation pulmonaire pendant une chirurgie thoracique assistée par vidéoscopie. Récemment, un affaissement pulmonaire plus rapide avec un BB qu'avec un TET-DL a été documenté. Les mécanismes physiologiques derrière cet affaissement plus rapide demeurent inconnus. Notre objectif était de mesurer l'absorption de l'air ambiant (Vresorb) et la pression intra-bronchique (Paérienne) dans le poumon non ventilé pendant la ventilation à un poumon en utilisant un TET-DL et un BB. MéTHODE: Les patients subissant une chirurgie thoracique assistée par vidéoscopie et recevant une ventilation unipulmonaire à l'aide d'un TET-DL ou d'un BB pour une résection pulmonaire ont été aléatoirement assignés à des mesures de Vresorb ou Paérienne dans le poumon non ventilé. RéSULTATS: Trente-neuf patients ont été inclus dans les analyses. La Vresorb moyenne (erreur-type sur la moyenne) était similaire dans les groupes TET-DL et BB [504 (85) vs 630 (86) mL, respectivement; différence moyenne, 126; intervalle de confiance [IC] 95 %, -128 à 380; P = 0,31]. La Paérienne moyenne (erreur-type sur la moyenne) est devenue progressivement négative dans le poumon non ventilé dans les groupes TET-DL et BB en atteignant [-20 (5) et -31 (10) cmH2O, respectivement; différence moyenne, -11; IC 95 %, -34 à 12; P = 0,44] au moment de l'ouverture de la plèvre. CONCLUSION: Pendant la ventilation unipulmonaire avant l'incision de la plèvre, un appel d'air ambiant dans le poumon non ventilé se produit quand la portion du dispositif d'isolation pulmonaire est maintenue ouverte. Ce phénomène peut être évité en occluant la lumière du dispositif d'isolation pulmonaire avant l'ouverture de la plèvre, ce qui entraînera une accumulation progressive de pression négative dans le poumon non ventilé. De futures études cliniques sont nécessaires pour confirmer ces résultats physiologiques et leur impact sur l'affaissement pulmonaire et les devenirs opératoires. ENREGISTREMENT DE L'éTUDE: www.clinicaltrials.gov (NCT02919267); enregistrée le 28 septembre 2016.

Non-ventilated lung deflation during one-lung ventilation with a double-lumen endotracheal tube: a randomized-controlled trial of occluding the non-ventilated endobronchial lumen before pleural opening.

PURPOSE: Lung deflation during one-lung ventilation (OLV) is thought to be faster using a double-lumen endotracheal tube (DL-ETT) than with a bronchial blocker, especially when the non-ventilated lumen is opened to allow egress of air from the operative lung. Nevertheless, ambient air can also be entrained into the non-ventilated lumen before pleural opening and subsequently delay deflation. We therefore hypothesized that occluding the non-ventilated DL-ETT lumen during OLV before pleural opening would prevent air entrainment and consequently enhance operative lung deflation during video-assisted thoracoscopic surgery (VATS). METHODS: Thirty patients undergoing VATS using DL-ETT to allow OLV were randomized to having the lumen of the operative lung either open (control group) or occluded (intervention group) to ambient air. The primary outcome was the time to lung collapse evaluated intraoperatively by the surgeons. The T50, an index of rate of deflation, was also determined from a probabilistic model derived from intraoperative video clips presented in random order to three observers. RESULTS: The median [interquartile range] time to lung deflation occurred faster in the intervention group than in the control group (24 [20-37] min vs 54 [48-68] min, respectively; median difference, 30 min; 95% confidence interval [CI], 14 to 46; P < 0.001). The estimated T50 was 32.6 min in the intervention group compared with 62.3 min in the control group (difference, - 29.7 min; 95% CI, - 51.1 to - 8.4; P = 0.008). CONCLUSION: Operative lung deflation during OLV with a DL-ETT is faster when the operative lumen remains closed before pleural opening thus preventing it from entraining ambient air during the closed chest phase of OLV. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT03508050); registered 27 September 2017.

RéSUMé: OBJECTIF: On pense que la déflation pulmonaire pendant la ventilation unipulmonaire (VUP) est plus rapide à l'aide d'un tube endotrachéal à double lumière (TET-DL) qu'avec un bloqueur bronchique, surtout lorsque la lumière non ventilée est ouverte pour permettre l'évacuation de l'air du poumon opéré. Néanmoins, l'air ambiant peut également être entraîné dans la lumière non ventilée avant l'ouverture pleurale et ainsi retarder la déflation. Nous avons donc émis l'hypothèse que l'occlusion de la lumière non ventilée du TET-DL pendant la VUP avant l'ouverture de la plèvre empêcherait l'entraînement d'air et accélérerait par conséquent la déflation du poumon opéré pendant une chirurgie thoracoscopique vidéo-assistée (VATS). MéTHODE: Trente patients subissant une VATS avec un TET-DL pour permettre une VUP ont été randomisés à une ouverture (groupe témoin) ou à une occlusion (groupe intervention) de la lumière du poumon opéré à l'air ambiant. Le critère d'évaluation principal était le temps jusqu'au collapsus du poumon tel qu'évalué pendant l'opération par les chirurgiens. Le T50, un indice du taux de déflation, a également été déterminé à partir d'un modèle probabiliste dérivé de clips vidéo peropératoires présentés de façon randomisée à trois observateurs. RéSULTATS: Le temps médian [écart interquartile] jusqu'à la déflation du poumon était plus court dans le groupe d'intervention que dans le groupe témoin (24 [20-37] min vs 54 [48-68] min, respectivement; différence médiane, 30 min; intervalle de confiance [IC] à 95 %, 14 à 46; P < 0,001). Le T50 estimé était de 32,6 min dans le groupe d'intervention comparativement à 62,3 min dans le groupe témoin (différence, -29,7 min; IC 95 %, -51,1 à -8,4; P = 0,008). CONCLUSION: La déflation du poumon opéré pendant une VUP avec un TET-DL est plus rapide quand la lumière opératoire reste fermée avant l'ouverture pleurale, l'empêchant ainsi d'entraîner l'air ambiant pendant la phase pré ouverture pleurale de la VUP. ENREGISTREMENT DE L'éTUDE: www.clinicaltrials.gov (NCT03508050); enregistrée le 27 septembre 2017.

Right upper lobe anatomy revisited: a computed tomography scan study.

BACKGROUND: The double lumen tube (DLT) has become the most popular way to isolate the lungs for thoracic surgery. The variable anatomy of the right main stem bronchus (RMSB) seems to be the main reason clinicians are unwilling to use the right-sided DLT (R-DLT). The factors that could compromise the adequate ventilation of the right lung are mostly the variable length of the RMSB and the misalignment of the lateral orifice of the R-DLT in regard to the right upper lobe bronchus (RULB). The objectives of this study were to validate an alternative method to estimate the RMSB length, and to determine the distribution of the angulation of the ostium of the RULB. METHODS: From high-resolution computed tomography scans of the thorax of 106 consecutive patients, the length of the RMSB was measured using Kim's method and the carina-to-carina method. The angle between the RULB origin and the lateral aspect of the RMSB was also measured. All these measurements were correlated and inter-observer variation documented. RESULTS: From the Kim's method, the mean (standard deviation [SD]) length of the RMSB was 25.5 (4.7) mm. From the alternative carina-to-carina method, the mean (SD) length of RMSB was 29.4 (4.6) mm. The inter-observer agreement was substantial with both methods (Kim's method: intraclass correlation coefficient [ICC] = 0.84; carina-to-carina method: ICC = 0.95). Both measures were closely related (ICC = 0.93; P < 0.001). The RULB presented a wide range angulation [mean (SD), 0.1 (9.5)°; range, -28.6 to 21.2]. CONCLUSION: These anatomic observations provide a better understanding of the variable anatomy of the right bronchial tree and may guide thoracic anesthesiologists in the choice of the best lung isolation device for their patients.

RéSUMé: CONTEXTE: Le tube double lumière (TDL) est actuellement la modalité la plus populaire pour isoler les poumons lors d'une chirurgie thoracique. L'anatomie variable de la bronche souche droite (BSD) semble être la principale raison qui freine l'engouement des cliniciens à utiliser un TDL droit (TDL-d). Les facteurs pouvant compliquer la ventilation adéquate du poumon droit sont surtout la longueur variable de la BSD et le mauvais alignement entre l'orifice latéral du TDL-d et de la bronche lobaire supérieure droite (BLSD). Les objectifs de cette étude étaient de valider une méthode alternative d'estimation de la longueur de la BSD ainsi que de déterminer la distribution de l'angulation de l'orifice de la BLSD. MéTHODE: En nous basant sur des images de tomodensitométrie (TDM) thoracique haute résolution de 106 patients consécutifs, la longueur de la BSD a été mesurée à l'aide de la méthode de Kim et de la méthode de carène à carène. L'angle entre l'origine de la BLSD et l'aspect latéral de la BSD a également été mesuré. Toutes ces mesures ont ensuite été corrélées et la variation inter-observateur documentée. RéSULTATS: En se fondant sur la méthode de Kim, la longueur moyenne (écart type [ÉT]) de la BSD était de 25,5 (4,7) mm. En se fondant sur la méthode alternative de carène à carène, la longueur moyenne (ÉT) de la BSD était de 29,4 (4,6) mm. La concordance inter-observateur était élevée lors de l'utilisation des deux méthodes (méthode de Kim : coefficient de corrélation intraclasse [CCI] = 0,84; méthode carène à carène : 0,95). Les deux mesures étaient très rapprochées (CCI = 0,93; P < 0,001). La BLSD présentait une angulation très variable [(ÉT) moyen, 0.1 (9,5)°; éventail, -28,6 à 21,2]. CONCLUSION: Ces observations anatomiques nous permettent de mieux comprendre l'anatomie variable de l'arbre bronchique droit et pourrait aider les anesthésiologistes thoraciques à choisir le dispositif le mieux adapté pour isoler le poumon de leur patient.

Effect of position and positive pressure ventilation on functional residual capacity in morbidly obese patients: a randomized trial.

PURPOSE: In morbidly obese patients, the position and ventilation strategy used during pre-oxygenation influence the safe non-hypoxic apnea time and the functional residual capacity (FRC). In awake morbidly obese volunteers, we hypothesized that the FRC would be higher after a five-minute period of positive pressure ventilation compared with spontaneous ventilation at zero inspiratory pressure. METHODS: Using a prospective crossover randomized trial design, obese subjects underwent, in a randomized order, a combination of one of three positions, supine (S), beach chair (BC), and reverse Trendelenburg (RT), and one of two ventilation strategies, spontaneous ventilation at zero inspiratory pressure (ZEEP-SV) or with positive pressure (PP-SV) set to an inspiratory pressure of 8 cmH2O, positive end-expiratory pressure of 10 cmH2O, and fraction of inspired oxygen of 0.21. RESULTS: Seventeen obese volunteers with a mean (standard deviation; SD) body mass index of 50 (8) kg·m-2 were included. Mean (SD) FRC in the three positions (S, BC, RT) was significantly higher using PP-SV compared with ZEEP-SV [2571 (477) vs 2215 (481) mL, respectively; mean difference, 356; 95% confidence interval (CI), 209 to 502; P < 0.001]. Mean (SD) FRC was significantly higher in the RT compared with BC position [2483 (521) vs 2338 (469) mL, respectively; mean difference, 145; 95% CI, 31 to 404; P = 0.01], while there was no difference between S and BC [2359 (519) mL vs 2338 (469) mL, respectively; mean difference, 21; 95% CI, -93 to 135; P = 0.89]. CONCLUSION: In awake morbidly obese volunteers, an increase in the FRC is observed when spontaneous ventilation at zero inspiratory pressure is switched to positive pressure. Compared with S positioning, the BC position had no measurable impact on the FRC. The RT position resulted in an optimal FRC. TRIAL REGISTRATION: clinicaltrials.gov (NCT02121808). Registered 24 April 2014.

Bronchial blocker versus left double-lumen endotracheal tube in video-assisted thoracoscopic surgery: a randomized-controlled trial examining time and quality of lung deflation.

INTRODUCTION: Double-lumen endotracheal tubes (DL-ETT) and bronchial blockers (BB) have both been used for lung isolation in video-assisted thoracic surgery (VATS). Though not well studied, it is widely thought that a DL-ETT provides faster and better quality lung collapse. The aim of this study was to compare a BB technique vs a left-sided DL-ETT strategy with regard to the time and quality of lung collapse during one-lung ventilation (OLV) for elective VATS. METHODS: Forty patients requiring OLV for VATS were randomized to receive a BB (n = 20) or a left-sided DL-ETT (n = 20). The primary endpoint was the time from pleural opening (performed by the surgeon) until complete lung collapse. The time was evaluated offline by reviewing video recorded during the VATS. The quality of lung deflation was also graded offline using a visual scale (1 = no lung collapse; 2 = partial lung collapse; and 3 = total lung collapse) and was recorded at several time points after pleural incision. The surgeon also graded the time to complete lung collapse and quality of lung deflation during the procedure. The surgeon's guess as to which device was used for lung isolation was also recorded. RESULTS: Of the 40 patients enrolled in the study, 20 patients in the DL-ETT group and 18 in the BB group were analyzed. There mean (standard deviation) time to complete lung collapse of the operative lung was significantly faster using the BB compared with using the DL-ETT [7.5 (3.8) min vs 36.6 (29.1) min, respectively; mean difference, 29.1 min; 95% confidence interval, 1.8 to 7.2; P < 0.001]. Overall, a higher proportion of patients in the BB group than in the DL-ETT group achieved a quality of lung collapse score of 3 at five minutes (57% vs 6%, respectively; P < 0.004), ten minutes (73% vs 14%, respectively; P = 0.005), and 20 min (100% vs 25%, respectively; P = 0.002) after opening the pleura. The surgeon incorrectly guessed the type of device used in 78% of the BB group and 50% of the DL-ETT group (P = 0.10). CONCLUSION: The time and quality of lung collapse during OLV for VATS was significantly better when using a BB than when using a left-sided DL-ETT. Surgeons could not reliably determine which device was being used based on the time and quality of lung collapse. This trial was registered at ClinicalTrials.gov number, NCT01615263.

Population pharmacokinetics of lidocaine administered during and after cardiac surgery.

OBJECTIVE: The objective of this study was to determine the pharmacokinetics of lidocaine in a 48-hour infusion in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). DESIGN: A retrospective substudy of a clinical trial assessing the efficacy of intravenous lidocaine for postoperative cognitive decline. SETTING: A university hospital. PARTICIPANTS: Ninety-nine patients undergoing cardiac surgery with CPB. INTERVENTIONS: After the induction of anesthesia, lidocaine was administered as a bolus of 1 mg/kg and followed by a continuous infusion at 4 mg/min for the 1st hour, 2 mg/min for the 2nd hour, and 1 mg/min for the next 46 hours. MEASUREMENTS AND MAIN RESULTS: Blood samples were taken at baseline, the end of CPB, and 24 and 48 hours after CPB for the measurement of the plasma concentration of lidocaine. Lidocaine levels increased significantly over time despite a constant rate of infusion (p < 0.05). The pharmacokinetics of lidocaine was best described by a 2-compartment model, and body weight was found to be a significant factor for the volume of the central compartment and clearance. The final pharmacokinetic parameters were V(1)(L) = 0.0619*weight, V(2)(L) = 187, CL(1) (L/min) = 0.00419*weight, and CL(2) (L/min) = 8.92. CONCLUSIONS: A 2-compartment pharmacokinetic model best describes the plasma concentrations of a 48-hour lidocaine infusion in patients undergoing cardiac surgery with CPB. The inclusion of body weight as a covariate on clearance and central compartment improves the model. Lidocaine infusions should be dosed by body weight and decreased after 24 hours to avoid potential toxicity in long-term infusions.

High frequency ventilation combined with spontaneous breathing during bronchopleural fistula repair: a case report.

PURPOSE: We report the addition of high frequency oscillatory ventilation (HFOV), combined with spontaneous breathing under general anesthesia, during an uncommon technique to occlude a late post-pneumonectomy bronchopleural fistula. CLINICAL FEATURES: A 41-year-old woman underwent an extended right pneumonectomy with chest wall resection and prosthetic reconstruction for a large adenocarcinoma of the upper lobe (T3N0M0). Her postoperative recovery was satisfactory, and she subsequently received adjuvant chemotherapy. Four months later, however, she was readmitted for investigation of confusion and pink expectorations. On cerebral magnetic resonance imaging, a frontal metastasis with surrounding edema was discovered, as well as a possible secondary lesion in the occipital lobe. In view of the comorbidities, thoracoscopy was planned as an interim measure, with the goal being to debride the fistula and to seal the prosthetic plug. During this case, a HFOV system was used to allow an addition of 2.5 L.min(-1) of minute ventilation to the patient's spontaneous respiration, while maintaining eucapnia without increasing airway pressure. CONCLUSIONS: With the addition of high frequency ventilation under general anesthesia in a patient with a persistent bronchopleural fistula, the PaCO(2) level was adequately controlled during the simultaneous use of fibreoptic bronchoscopy and video assisted thoracoscopy to facilitate a successful surgical repair.

Predicting postoperative pain by preoperative pressure pain assessment.

BACKGROUND: The goal of this study was to evaluate whether preoperative pressure pain sensitivity testing is predictive of postoperative surgical pain. METHODS: Female subjects undergoing lower abdominal gynecologic surgery were studied. A pressure algometer was used preoperatively to determine the pressure pain threshold and tolerance. A visual analog scale (VAS) was used to assess postoperative pain. A State-Trait Anxiety Inventory was used to assess patients' anxiety. Subjects received intravenous patient-controlled analgesia for postoperative pain control. The preoperative pain threshold and tolerance were compared with the postoperative VAS pain score and morphine consumption. RESULTS: Forty women were enrolled. Their preoperative pressure pain threshold and tolerance were 141 +/- 65 kPa and 223 +/- 62 kPa, respectively. The VAS pain score in the postanesthesia care unit and at 24 h postoperatively were 81 +/- 24 and 31 +/- 10, respectively. Highly anxious patients had higher VAS pain scores in the postanesthesia care unit (P < 0.05). Pressure pain tolerance was significantly correlated with the VAS at 24 h postoperatively (P < 0.001, r = -0.52). Pressure pain tolerance after fentanyl administration (mean, 272 +/- 68 kPa) correlated significantly with morphine consumption in the first 24 h postoperatively (P < 0.002, r = -0.48). CONCLUSIONS: Assessment of preoperative pressure pain tolerance is significantly correlated with the level of postoperative pain. Pain tolerance assessment after fentanyl was administered and fentanyl sensitivity predicted the dose of analgesics used in the first 24 h after surgery. The algometer is thus a simple, useful tool for predicting postoperative pain and analgesic consumption.

Changes in hematocrit based on incremental blood sampling: mathematical models perform poorly.

PURPOSE: Excessive blood sampling, with its inherent risks, is of growing concern among clinicians. We performed this study to measure the changes in hematocrit (Hct) during a laboratory investigation where multiple blood samples are collected. The performance of a simple mathematical model, used in clinical practice to predict Hct changes, is evaluated. METHODS: Eight healthy male volunteers participated in this study. The equation Hct(f) = Hct(i)*(EBV-BL)/EBV is used to predict changes in Hct. Where Hct(f) and Hct(i) are, respectively, the final and initial Hct, EBV is the estimated blood volume and BL is the blood loss. RESULTS: Thirty-five pharmacokinetic samples per subject were collected totalling 314 mL of BL. The Hct decreased from 44.2% +/- 2.2% to 39.9% +/- 2.5% (P = 0.001). On average, model predictions tended to have a discrete tendency to underestimate the Hct changes (-0.5% points of bias). While the predictions of the Hct were very accurate in 50% of the subjects, the discrepancy of the Hct predictions was clinically significant in the other 50% of the subjects. CONCLUSION: Consistent with the model prediction, this study demonstrated a significant reduction in the Hct values in healthy subjects undergoing incremental phlebotomy. On average, the model successfully predicted the decrease in Hct. However, the inter- and intra-individual variabilities in the Hct changes are clinically significant. In clinical settings, which are not well controlled environments, the variability is likely to be greater and the clinical use of the model cannot replace the need to monitor the Hct.

Dexmedetomidine pharmacodynamics: part I: crossover comparison of the respiratory effects of dexmedetomidine and remifentanil in healthy volunteers.

BACKGROUND: Dexmedetomidine, a highly selective alpha2-adrenoceptor agonist used for short-term sedation of mechanically ventilated patients, has minimal effect on ventilation. METHODS: This study compared the respiratory effect of dexmedetomidine to that of remifentanil. The authors measured and compared respiratory responses of six healthy male volunteers during (1) a stepwise target-controlled infusion of remifentanil, (2) a stepwise target-controlled infusion of dexmedetomidine, and (3) a pseudonatural sleep session. RESULTS: Compared with baseline, remifentanil infusions resulted in respiratory depression as evidenced by a decrease in respiratory rate and minute ventilation, respiratory acidosis, and apnea episodes resulting in desaturations. Remifentanil disturbed the natural pattern of breathing and flattened the distribution of ventilatory timing (inspiratory time/ventilatory cycle time). The respiratory effects of dexmedetomidine markedly contrasted with those of remifentanil. When compared with baseline, during dexmedetomidine infusions, the respiratory rate significantly increased, and the overall apnea/hypopnea index significantly decreased. The distribution of inspiratory time/ventilatory cycle time showed an increased peak. In addition, dexmedetomidine seemed to mimic some aspect of natural sleep. While the subjects were breathing a 5% CO2 mixture, hypercapnic arousal phenomena (documented by the Bispectral Index, the electroencephalogram, and sudden increase in the minute ventilation) were observed during dexmedetomidine infusions. Similar phenomena during natural sleep have been reported in the literature. CONCLUSIONS: In comparison with remifentanil, dexmedetomidine infusions (1) did not result in clinically significant respiratory depression, (2) decreased rather than increased the apnea/hypopnea index, and (3) exhibited some similarity with natural sleep.

Dexmedetomidine pharmacodynamics: Part II: Crossover comparison of the analgesic effect of dexmedetomidine and remifentanil in healthy volunteers.

BACKGROUND: Dexmedetomidine is a highly selective alpha2-adrenoceptor agonist used for short-term sedation of mechanically ventilated patients. The analgesic profile of dexmedetomidine has not been fully characterized in humans. METHODS: This study was designed to compare the analgesic responses of six healthy male volunteers during stepwise target-controlled infusions of remifentanil and dexmedetomidine. A computer-controlled thermode was used to deliver painful heat stimuli to the volar side of the forearms of the subjects. Six sequential 5-s stimuli (ranging from 41 degrees to 50 degrees C) were delivered in random order. The recorded visual analog scale was used to fit an Emax model. RESULTS: Compared to baseline, remifentanil infusions resulted in a right shift of the sigmoid curve (increased T50, the temperature producing a visual analog scale score of 50% of the maximal effect, from 46.1 degrees C at baseline to 48.4 degrees and 49.1 degrees C during remifentanil infusions) without a change of the steepness of the curve (identical Hill coefficients gamma during baseline and remifentanil). Compared to baseline, dexmedetomidine infusions resulted in both a right shift of the sigmoid curve (increased T50 to 47.2 degrees C) and a decrease in the steepness of the curve (decreased gamma from 3.24 during baseline and remifentanil infusions to 2.45 during dexmedetomidine infusions). There was no difference in the pain responses between baseline and after recovery from remifentanil infusions (identical T50 and gamma). CONCLUSION: As expected, dexmedetomidine is not as effective an analgesic as the opioid remifentanil. The difference in the quality of the analgesia with remifentanil may be a reflection of a different mechanism of action or a consequence of the sedative effect of dexmedetomidine.