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.

The Anesthetic Strategy for Patients with Mucopolysaccharidoses: A Retrospective Cohort Study.

Anesthesia for patients with mucopolysaccharidoses (MPS) is quite challenging due to vital systemic dysfunction following progressive accumulation of lysosomal glycosaminoglycans. Previous studies focused on perioperative difficult airway management under general anesthesia but rarely depicted the concern of choosing the size of the endotracheal tube (ETT) as well as neuraxial anesthesia. This study aimed to analyze the overall anesthetic management and related complications for a thorough anesthetic strategy. Within the study period from 2002 to 2021, each record of the anesthetic and perioperative quality assurance/improvement system for patients with a diagnosis of MPS at MacKay Memorial Hospital was retrospectively reviewed. A total of 51 individuals with 151 anesthesia for 163 interventions were cohort studied, and there were 136 general anesthesia and 15 neuraxial anesthesia. We found that the most common interventions for MPS patients were otolaryngological surgeries (49.6%). Additionally, a secured airway played a marked preference for the most general anesthesia (87.1%). The incidence of difficult intubation was 12.5%. In view of ETT size, a smaller than estimated size was used in MPS type II, III, IV, and VI patients and also in patients who received intubation with multiple attempts. However, a larger than estimated size of ETT was adopted whilst choosing cuffed ones. For neuraxial anesthesia, two failed spinal anesthesia procedures were converted to general anesthesia and 73 percent of the patients received perioperative sedation. In conclusion, through the individualized anesthetic strategy and build-up of an experienced team for airway management, high-quality anesthesia can be ensured in each patient.

Effect of the infusion rate of propofol on the onset time of rocuronium.

BACKGROUND: Administration of propofol, especially rapid administration, decreases patient cardiac output (CO) to various degrees. CO might influence the buildup of an effective drug level within the neuromuscular junction and affect the onset time of neuromuscular blockers. The present study aimed to investigate the effects of different infusion rates of propofol on patient CO and the onset time of rocuronium. METHODS: A total of 90 patients were randomly assigned to receive propofol (2.5 mg/kg) at an infusion rate of 480 mg/min (group A), 240 mg/min (group B), or 120 mg/min (group C). After the administration of propofol, rocuronium (0.6 mg/kg) was administered to facilitate tracheal intubation. The Finometer monitor was used to obtain the cardiovascular profile during the induction of general anesthesia. Neuromuscular relaxation was monitored by acceleromyography using the ulnar nerve at the wrist surface and electrodes with repeated single twitches. Onset time was defined as the time from the beginning of rocuronium injection until 95% twitch depression. The onset time of rocuronium in the three groups was compared using analysis of variance with the post-hoc Tukey test. A p-value <0.05 was considered statistically significant. RESULTS: After induction, a significant decrease in CO was observed in group A (21.6% ± 4.6%) when compared with the findings in group B (11.6% ± 4.5%) and group C (9.8% ± 4.6%). The onset time of rocuronium was significantly longer in group A (177.7 ± 17.6 seconds) than in group B (121.3 ± 18.3 seconds) and group C (118.3 ± 12.3 seconds). CONCLUSION: Rapid administration of propofol significantly delays the onset time of rocuronium by altering CO as measured with the Finometer monitor.

Preoperative measurement of maternal abdominal circumference relates the initial sensory block level of spinal anesthesia for cesarean section: An observational study.

OBJECTIVE: Lumbosacral cerebrospinal fluid volume is decreased as the enlarging uterus compresses the inferior vena cava during pregnancy. A subsequent greater cephalad spread of sensory blockade is observed. Gravid uterus plays a crucial role in affecting the spinal anesthesia level. We hypothesized that maternal abdominal circumference can reflect compressive effect of the uterus and investigated the relationship between abdominal circumference and the level of sensory blockade, and incidence of hypotension following spinal anesthesia with hyperbaric bupivacaine in term parturients. MATERIALS AND METHODS: Forty-two term parturients scheduled for elective cesarean section were studied. Abdominal circumference was measured before spinal anesthesia; 0.5% hyperbaric bupivacaine (2 mL, 2.2 mL, or 2.4 mL) was injected in to the subarachnoid space at the L3-L4 intervertebral level according to the parturient's height. The level of sensory blockade was assessed using an ice cube 1 minute, 5 minutes, 10 minutes, and 15 minutes after the spinal injection. The level of sensory blockade at the 15th minute was defined as the level of maximum sensory blockade. Statistical correlation coefficients were evaluated with Spearman's rank correlation. RESULTS: The correlation coefficient between the abdominal circumference and spinal level measured by cold sensation loss at 5 minutes after spinal anesthesia was significantly positive (right side ρ=0.43, p=0.005; left side ρ=0.46, p=0.003). No significant correlation was found between abdominal circumference and the level of maximum sensory blockade, the incidence of hypotension, ephedrine dosage, nausea, and vomiting after spinal anesthesia. CONCLUSION: Parturients with greater abdominal circumference value have a higher level of sensory blockade at 5 minutes after spinal anesthesia. Abdominal circumference cannot predict the maximum sensory blockade level and the incidence of hypotension.

Local anesthetics induce apoptosis in human breast tumor cells.

BACKGROUND: Previous studies have shown that local anesthetics may induce apoptosis in some cell types. In this study, we investigated the apoptotic effects of local anesthetics in human breast tumor cells. METHODS: Human breast cancer (MCF-7) and mammary epithelial (MCF-10A) cell lines were treated with lidocaine and/or bupivacaine. Cell viability, DNA fragmentation, and annexin V immunofluorescence staining were assessed. The effects on apoptosis-related protein expression were investigated by Western blot analysis. The findings were extended to studies in an in vivo xenograft model. RESULTS: Treatment of breast tumor cells with lidocaine and bupivacaine resulted in inhibition of cell viability via induction of apoptosis. The effects were more prominent in MCF-7 cells than in MCF-10A cells. Treatment with local anesthetics induced caspase 7, 8, 9, and poly ADP-ribose polymerase cleavage. The cleavage of caspase 7 and poly ADP-ribose polymerase induced by local anesthetics were effectively blocked by caspase inhibitors. Furthermore, treatment of MCF-7 xenografts with local anesthetics resulted in higher expression of cleaved caspase 7 and an increase in terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. CONCLUSION: Lidocaine and bupivacaine induce apoptosis of breast tumor cells at clinically relevant concentrations. Our results reveal previously unrecognized beneficial actions of local anesthetics and call for further studies to assess the oncologic advantages of their use during breast cancer surgery.

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.

Ultrasound-guided ganglion impar block: a technical report.

BACKGROUND AND OBJECTIVES: Ganglion impar block is an uncommon procedure that has been performed traditional with fluoroscopy. One approach is the trans-sacrococcygeal approach. Sometimes this can be difficult because the sacrococcygeal joint (SCJ) cannot be readily seen on anteroposterior (AP) and lateral fluoroscopy. This technical report describes the feasibility of ultrasound in assisting ganglion impar blocks. METHODS: We performed ganglion impar block using ultrasound as the primary imaging tool, with fluoroscopic confirmation in 15 patients. We used a linear array transducer (5-12 MHz) to obtain sonographic transverse and longitudinal views at the sacral cornua; we identified the first cleft below the sacral hiatus as the SCJ. Then we inserted a 23-gauge (7 cm in length) needle into the SCJ under sonographic guidance. Then we confirmed proper needle depth by lateral fluoroscopy and injection of contrast agent. RESULTS: In all 15 procedures, we accurately located and passed the needle into the patients' SCJs under real time sonographic guidance. CONCLUSIONS: In cases where the cleft cannot be readily seen on AP and lateral fluoroscopy, we have found ultrasound to be of assistance. Ultrasound does not replace fluoroscopy, because lateral fluoroscopy is still required to establish safe depth, and correct site of injection. However, ultrasound can be helpful when fluoroscopy alone is insufficient.

Anesthetic management of a patient with congenital methemoglobinemia.

Methemoglobinemia occasionally causes cyanosis particularly in congenital methemoglobinemia. Avoidance of exposure to oxidizing agents is important for patients with congenital methemoglobinemia because of their deficient enzymatic pathways and decreased oxygen-carrying capacity. Here, we present a patient with preoperatively undiagnosed congenital methemoglobinemia who underwent uterine myomectomy under general anesthesia. The patient was a 35-year-old woman who displayed a low pulse oximetry reading of 91% prior to induction of anesthesia. Methemoglobinemia was first suspected intraoperatively because of a mismatch of SpO2 of finger pulse oximetry and SaO2 of arterial blood, and was later confirmed by multiple-wavelength CO-oximetry. The pathophysiology, etiology, clinical manifestations, anesthetic considerations, and treatment options of methemoglobinemia are discussed.

The influence of age on the dynamic relationship between end-tidal sevoflurane concentrations and bispectral index.

BACKGROUND: Age is an important determinant of the pharmacokinetic profile of inhaled anesthetics. The influence of age on the dynamic profile of sevoflurane's effect has not been well described. We performed this study to characterize the influence of age and other covariates on the dynamic relationship between sevoflurane end-tidal concentration (C(ET)) and its effect measured by bispectral index (BIS). METHODS: Fifty patients, aged 3-71 yr, scheduled for minor surgery were prospectively studied. The BIS and sevoflurane C(ET) were continuously measured during the study period. During maintenance of anesthesia and after stable BIS values of 60-65 were obtained, the inspired concentration of sevoflurane was increased to 5 vol % for 5 min or until BIS <40 and then decreased. The dynamic relationship between sevoflurane C(ET) and its effect as measured by BIS during this transition period were modeled with an inhibitory E(max) model using a population pharmacokinetic-pharmacodynamic approach with NONMEM V. A predictive check method was used to validate the final model. RESULTS: The sensitivity to sevoflurane's effect as measured by BIS expressed in the C(50) [steady-state C(ET) eliciting half of maximum response (I(max))] increased with age. The speed of change of sevoflurane's effect, expressed as the effect-site equilibration half-life (t(1/2) k(e0)), increased at older ages. The predictive check analysis confirmed the adequacy of the model. CONCLUSIONS: Age significantly affects the dynamic relationship between sevoflurane C(ET) and its effect measured with BIS.

Premedication with mirtazapine reduces preoperative anxiety and postoperative nausea and vomiting.

BACKGROUND: Mirtazapine is a new antidepressant that blocks 5-HT2 and 5-HT3 receptors. With this receptor profile, it is possible that mirtazapine could provide both anxiolysis and efficacy for postoperative nausea and vomiting (PONV). We therefore tested the hypothesis that premedication with mirtazapine can reduce preoperative anxiety and PONV. METHODS: Eighty female patients with at least two PONV risk factors scheduled for gynecological surgery were enrolled. Dexamethasone 8 mg was given before induction of anesthesia and patients were randomly assigned to group M + D (mirtazapine plus dexamethasone) or group dexamethasone. An oral disintegrating mirtazapine 30 mg or placebo tablet was given 1 h before surgery. Preoperative anxiety level was assessed by a visual analog scale (VAS) before mirtazapine administration and 1 h thereafter. General anesthesia was induced with 1% propofol at the rate of 200 mL/h (until loss of consciousness) and was then maintained with sevoflurane in oxygen and air. An auditory evoked potentials index monitor was used to titrate sevoflurane. The incidence of PONV, the use of rescue antiemetic, complete response, postoperative Ramsay Sedation Scores, and VAS pain scores were assessed 1, 2, and 24 h after surgery and compared. RESULTS: The VAS anxiety scale was lower in group M + D after mirtazapine administration. There were no differences in the induction dose of propofol, the concentrations of sevoflurane during anesthesia, and recovery times between the two groups. The incidence of complete response to PONV over 0-24 h was lower in group M + D (80% vs 50%, P < 0.01). CONCLUSIONS: Premedication with mirtazapine 30 mg reduces the level of preoperative anxiety and the risk of PONV in moderate and high-risk female patients.

Simulation analysis of the performance of target-controlled infusion of propofol in Chinese patients.

BACKGROUND: The performance of target-controlled infusion (TCI) devices is important for the safety of patients. This study examined the performance of two propofol pharmacokinetic parameter sets in Chinese patients by computer simulation. METHODS: Two sets of propofol pharmacokinetic parameters respectively derived from Marsh's and Schnider's studies were compared with those obtained in Chinese subjects from Li's study. Pharmacokinetic parameters of propofol from Li's study for subjects of three different entities (average adult, obese adult, and elderly) were used to estimate the performance of Marsh's and Schnider's models. Sixty virtual patients were generated with Li's parameters. A computer program, STANPUMP, was used to perform the pharmacokinetic simulation. An induction dose of propofol at 2 mg/kg for average or obese adult, while 1.5 mg/kg for the elderly, followed by TCI of 4 microg/mL (average and obese adult) or 3 microg/mL (elderly) were simulated. The infusion schemes generated by STANPUMP using Marsh's or Schnider's model were put in to simulate the predicted plasma concentration based on the pharmacokinetic parameters from Li's study. The median performance error (MDPE) and absolute median performance error (MDAPE) were calculated to estimate the bias and inaccuracy. Differences between models were calculated using the paired t test. A P value < 0.05 was considered statistically significant. RESULTS: The bias and inaccuracy by Marsh's model in average adults were -11.9% and 18.5% respectively and by Schnider's model were -8.6% and 17.9%. For obese adults, the bias and inaccuracy were 6.3% and 26.2% respectively for Marsh's model and -6.6% and 22.6% for Schnider's model. Sohnider's model resulted in a significantly greater inaccuracy than Marsh's model (42.1% versus 15.5%) when applied to elderly patients. CONCLUSIONS: The performance of TCI infusion of propofol in Chinese patients is generally acceptable with Marsh's or Schnider's model apart from using Schnider's model in Chinese elderly patients. Further study to investigate the difference of propofol pharmacokinetics between Chinese and non-Chinese elderly patients is necessary.

Changes of regional cerebral oxygen saturation during spinal anesthesia.

BACKGROUND: During spinal anesthesia, hemodynamic status is routinely monitored, but this may not give an accurate assessment of cerebral oxygenation. Cerebral oximetry, facilitated by using a near-infrared spectroscope, is a way of estimating regional cerebral oxygen saturation (SrO2). We designed this prospective clinical study to determine whether the changes in mean arterial pressure (MAP) and heart rate (HR) could predict changes in SrO2 during spinal anesthesia. METHODS: The study sample available for analysis included 45 patients, ASA class I to II, who were scheduled for elective ureteroscopic surgery requiring spinal anesthesia. Spinal anesthesia was performed with 12 mg 0.5% hyperbaric bupivacaine injected intrathecally via L3-4 or L4-5 interspace. MAP, HR, oxygen saturation by pulse oximeter, and SrO2 by near-infrared spectroscope were recorded every 2 min throughout the procedure. RESULTS: SrO2 was tested by the Shapiro-Wilk test and the results departed from the multivariate normal distribution. The method of generalized estimating equations (GEE) was then used to estimate the model. The output of the GEE analysis for the time-lag model showed that there were relationships between SrO2 and two predictors (MAP and HR) with the correction of the baseline values. All the parameters were significant at a level of 5%. The effects of the decreases of MAP and HR on SrO2 lasted continuously for at least 6 min. CONCLUSIONS: Based on the time-lag pattern between two predictors (MAP and HR) and SrO2 during spinal anesthesia, we ventured to conclude that a change in MAP or HR caused a significant decrease in SrO2. Since no patient developed any neurologic complication perioperatively, further study must be performed to elucidate the clinical importance of our findings.

Postoperative delayed respiratory failure caused by Guillain-Barré syndrome--a case report.

Postoperative respiratory failure caused by Guillain-Barré syndrome (GBS) is a rare complication after general anesthesia. We report a GBS patient who after receiving an operation for polycystic liver disease under general anesthesia developed weakness of upper and lower extremities on the 3rd postoperative day, with decreased deep tendon reflex, which ultimately evolved into respiratory failure. Slurred speech and bilateral ptosis were also noted. All these manifested an acute peripheral polyneuropathy combined with bulbar involvement. According to the clinical picture, CSF examination and results of nerve conduction tests, Guillain-Barré syndrome was diagnosed. Plasmapheresis was immediately arranged and her motor weakness problem was soon improved after treatment. No neurological sequelae were found two months after discharge. Postoperative muscle weakness is usually caused by residual effects of anesthetic agents or surgical complications. But it may sometimes be related to some rare neurological diseases. To prompt an accurate diagnosis of Guillain-Barré syndrome is important because it can help forestall fatal complications. In addition, the prognosis will be encouraging with early treatment.

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.

The effect of hemodynamic changes induced by propofol induction on cerebral oxygenation in young and elderly patients.

STUDY OBJECTIVE: To investigate the difference of regional cerebral oxygen saturation (rSo2) decrease in response to the decrease in mean arterial blood pressure (MAP) in young and elderly patients. DESIGN: Prospective clinical study. SETTING: Medical center hospital. PATIENTS: Twenty-four American Society of Anesthesiologists physical status I and II patients, 12 of whom were young and the other 12 elderly, scheduled for elective surgery requiring general anesthesia. Patients received propofol 2 mg/kg (young patient group) and propofol 1.5 mg/kg (elderly patient group) as an induction drug. MEASUREMENTS: MAP and rSo2 were recorded continuously for 5 minutes after propofol administration. MAIN RESULTS: MAP values at the second to fifth minutes and rSo2 at the second minute after propofol administration were significantly lower than baseline in both groups (P<.05). The rSo2 decrease was minimal, and the slopes of the rSo2 decrease in response to the MAP decrease in the young and elderly groups were 0.093+/-0.012 (P<.001) and 0.112+/-0.016 (P<.001) (mean+/-SEM), respectively. CONCLUSIONS: After propofol induction, there was no difference between young and elderly patients in rSo2 decrease in response to the decrease in MAP.

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.