Effects of remifentanil/propofol in comparison with isoflurane on dynamic cerebrovascular autoregulation in humans

BACKGROUND: This study investigates the effects of remifentanil and propofol in comparison to isoflurane on dynamic cerebrovascular autoregulation in humans. METHODS: In 16 awake patients dynamic cerebrovascular autoregulation was measured using transcranial Doppler sonography (TCD). Thereafter patients were intubated, ventilated with O2/air (FiO2=0.33) and randomly assigned to one of the following anesthetic protocols: group 1 (n=8): 0.5 microg x kg(-1) x min(-1) remifentanil combined with a propofol-target plasma concentration of 1.5 microg x ml(-1) group 2 (n=8): 1.8 % isoflurane (1.5 MAC). Following 20 min of equilibration the autoregulatory challenge was repeated. Arterial blood gases and body temperature were maintained constant over time. Statistics: Mann-Whitney U-test and Wilcoxon signed-rank test. RESULTS: Dynamic autoregulation was intact in all patients prior to induction of anesthesia expressed by an autoregulatory index (ARI) of 5.4+/-1.21 (mean+/-SD, group 1) and 5.9+/-0.98 (mean+/-SD, group 2). With remifentanil/propofol anesthesia dynamic autoregulation was similar to the awake state (group 1: ARI=4.9+/-0.88). In contrast, autoregulatory response was delayed with 1.5 MAC isoflurane (group 2, ARI=2.1+/-0.92) (P<0.05). CONCLUSION: These data show that dynamic cerebrovascular autoregulation is maintained with remifentanil-based total intravenous anesthesia. This is consistent with the view that narcotics (and hypnotics) do not alter the physiologic cerebrovascular responses to changes in MAP. In contrast, 1.5 MAC isoflurane delays cerebrovascular autoregulation compared to the awake state.     

Caudal analgesia in children: S(+)-ketamine vs S(+)-ketamine plus clonidine

BACKGROUND: The aim of this study was to evaluate postoperative analgesia provided by caudal S(+)-ketamine and S(+)-ketamine plus clonidine without local anesthetic. METHODS: Forty-four children aged 1-5 years consecutively scheduled for inguinal hernia repair, hydrocele repair or orchidopexy were randomly assigned to receive a caudal injection of either S(+)-ketamine 1 mg x kg(-1) (group K) or S(+)-ketamine 0.5 mg x kg(-1) plus clonidine 1 microg x kg(-1) (group KC). Postoperative analgesia and sedation were evaluated by CHEOPS and Ramsay scale from emergence from general anesthesia for 24 h. RESULTS: No statistical difference was observed between study groups with respect to pain and sedation assessment. A slight trend toward a reduced requirement for rescue analgesia in group KC was observed, although not statistically significant. CONCLUSIONS: Caudal S(+)-ketamine 1 mg x kg(-1) and S(+)-ketamine 0.5 mg x kg(-1) plus clonidine 1 microg x kg(-1) are safe and provide effective postoperative analgesia in children without adverse effects.     

右旋氯胺酮在成年人临床麻醉中的应用

背景 右旋氯胺酮在欧美各国已广泛使用,与我国临床使用的消旋氯胺酮比较,其麻醉、镇痛效应更强,精神副反应及分泌物更少,苏醒时间更短.目的 综述右旋氯胺酮的临床应用,为该药在国内麻醉中的应用提供参考.内容 就右旋氯胺酮在麻醉诱导与维持、疼痛治疗、ICU的镇静镇痛及小儿麻醉等方面的临床应用进行归纳总结.趋向 使右旋氯胺酮更加安全、有效、广泛地应用于临床.     

S(+)-ketamine for rectal premedication in children

Our purpose for this prospective, randomized, and double-blinded study was to evaluate the anesthetic efficacy of S(+)-ketamine, an enantiomer of racemic ketamine, compared with a combination of S(+)-ketamine and midazolam, and plain midazolam for rectal premedication in pediatric anesthesia. Sixty-two children, ASA physical status I and II, scheduled for minor surgery, were randomly assigned to be given rectally one of the following: 1.5 mg/kg preservative-free S(+)-ketamine, a combination of 0.75 mg/kg preservative-free S(+)-ketamine and 0.75 mg/kg midazolam, or 0.75 mg/kg midazolam. Preoperative anesthetic efficacy was graded during a period of 20 min by using a five-point scale from 1 = awake to 5 = asleep. Tolerance during anesthesia induction via face mask was graded by using a four-point scale from 1 = very good to 4 = bad. A sufficient anesthetic level (> or = 3) after rectal premedication was reached in 86% in midazolam/S(+)-ketamine premedicated children, in 75% in midazolam premedicated children, but only in 30% in S(+)-ketamine premedicated children (P < 0.05 S(+)-ketamine versus midazolam/S(+)-ketamine and midazolam groups). The incidence of side effects after rectal premedication was rare. Whereas the mask acceptance score was comparable in the three study groups, a 25% rate of complications during anesthesia induction via face was observed in the S(+)-ketamine study group (P < 0.05 versus other study groups). Our conclusions are that S(+)-ketamine for rectal premedication in the dose we chose shows a poor anesthetic effect and a frequent incidence of side effects during induction of anesthesia via face mask compared with the combination of midazolam/S(+)-ketamine and plain midazolam. Dose-response studies of S(+)-ketamine for rectal premedication in pediatric anesthesia may be warranted.     

S(+)-ketamine for caudal block in paediatric anaesthesia

We have evaluated the intra- and postoperative analgesic efficacy of preservative-free S(+)-ketamine compared with bupivacaine for caudal block in paediatric hernia repair. After induction of general anaesthesia, 49 children undergoing hernia repair were given a caudal injection (0.75 ml kg-1) of S(+)-ketamine 0.5 mg kg-1 (group K1), S(+)- ketamine 1.0 mg kg-1 (group K2) or 0.25% bupivacaine with epinephrine 1:200,000 (group B). No additional analgesic drugs were required during operation in any of the groups. Haemodynamic and respiratory variables remained stable during the observation period. Mean duration of analgesia was significantly longer in groups B and K2 compared with group K1 (300 (SD 96) min and 273 (123) min vs 203 (117) min; P < 0.05). Groups B and K2 required less analgesics in the postoperative period compared with group K1 (30% and 33% vs 72%; P < 0.05). Postoperative sedation scores were comparable between the three groups. We conclude that S(+)-ketamine 1.0 mg kg-1 for caudal block in children produced surgical and postoperative analgesia equivalent to that of bupivacaine.      

右氯胺酮的药理学特点和临床应用

背景 右氯胺酮在欧洲已广泛使用,与常见的消旋氯胺酮比较,具有药效更强、可控性更好、副作用更少等优势. 目的 对右氯胺酮的药理学特点和目前的临床研究进行综述,为进一步研究和应用于临床提供参考. 内容 通过与常见的消旋氯胺酮比较,阐述右氯胺酮在药效、可控性、副作用等方面的优势.围术期小剂量应用右氯胺酮可减少术后额外镇痛药的用量,延长术后镇痛的时间,提高镇痛质量. 趋向 右氯胺酮可能在一些临床应用中取代消旋氯胺酮.     

S(+)-ketamine increases muscle sympathetic activity and maintains the neural response to hypotensive challenges in humans

BACKGROUND: S(+)-Ketamine is reported to exert twofold greater analgesic and hypnotic effects but a shorter recovery time in comparison with racemic ketamine, indicating possible differential effects of stereoisomers. However, cardiovascular regulation during S(+)-ketamine anesthesia has not been studied. Muscle sympathetic activity (MSA) may be an indicator of the underlying alterations of sympathetic outflow. Whether S(+)-ketamine decreases MSA in a similar manner as the racemate is not known. Thus, the authors tested the hypothesis that S(+)-ketamine changes MSA and the muscle sympathetic response to a hypotensive challenge. METHODS: Muscle sympathetic activity was recorded by microneurography in the peroneal nerve of six healthy participants before and during anesthesia with S(+)-ketamine (670 microg/kg intravenously followed by 15 microg x kg(-1) x min(-1)). Catecholamine and ketamine plasma concentrations, heart rate, and arterial blood pressure were also determined. MSA responses to a hypotensive challenge were assessed by injection of sodium nitroprusside (2-10 microg/kg) before and during S(+)-ketamine anesthesia. In the final step, increased arterial pressure observed during anesthesia with S(+)-ketamine was adjusted to preanesthetic values by sodium nitroprusside infusion (1-6 microg x kg(-1) x min(-1)). RESULTS: Anesthesia with S(+)-ketamine (ketamine plasma concentration 713 +/- 295 microg/l) significantly increased MSA burst frequency (mean +/- SD; 18 +/- 6 to 35 +/- 11 bursts/min) and burst incidence (32 +/- 10 to 48 +/- 15 bursts/100 heartbeats) and was associated with a doubling of norepinephrine plasma concentration (from 159 +/- 52 to 373 +/- 136 pg/ml) parallel to the increase in MSA. Heart rate and arterial blood pressure also significantly increased. When increased arterial pressure during S(+)-ketamine was decreased to awake values with sodium nitroprusside, MSA increased further (to 53 +/- 24 bursts/min and 60 +/- 20 bursts/100 heartbeats, respectively). The MSA increase in response to the hypotensive challenge was fully maintained during anesthesia with S(+)-ketamine. CONCLUSIONS: S(+)-Ketamine increases efferent sympathetic outflow to muscle. Despite increased MSA and arterial pressure during S(+)-ketamine anesthesia, the increase in MSA in response to arterial hypotension is maintained.     

The effects of large-dose propofol on cerebrovascular pressure autoregulation in head-injured patients

In healthy individuals, cerebrovascular pressure autoregulation is preserved or even improved when propofol is infused. We examined the effect of an increase in propofol plasma concentration on pressure autoregulation in 10 head-injured patients. Using target-controlled infusions, the static rate of autoregulation was determined at a moderate (2.3 +/- 0.4 microg/mL) and a large (4.3 +/- 0.04 microg/mL) plasma target concentration of propofol. Using norepinephrine to control cerebral perfusion pressure, transcranial Doppler measurements from the middle cerebral artery were made at a cerebral perfusion pressure of 70 and 85 mm Hg at each propofol concentration. Middle cerebral artery flow velocities at the large propofol concentration were significantly lower than at the moderate concentration, without any concurrent increase in arterio-jugular difference in oxygen content, a finding compatible with maintained flow-metabolism coupling. Despite this, static rate of autoregulation decreased significantly from 54% +/- 36% to 28% +/- 35% (P = 0.029). Our data suggest that after head injury, the cerebrovascular effects of propofol are different from those observed in healthy individuals. We propose that large doses of propofol should be used cautiously in head-injured patients, because there is the potential to increase the injured brain's vulnerability to secondary insults. IMPLICATIONS: Propofol is used for sedation and control of intracranial pressure in head-injured patients. In contrast to previous data from healthy individuals, we show a deterioration of cerebrovascular pressure autoregulation with fast propofol infusion rates after head injury. Large propofol doses may increase the injured brain's vulnerability to secondary insults.     

Analgesic effects of caudal and intramuscular S(+)-ketamine in children

BACKGROUND: Previous studies suggest that caudal administration of ketamine cause effective analgesia. The purpose of the current study was to compare the clinical effectiveness and plasma concentrations of S(+)-ketamine after caudal or intramuscular administration in children to distinguish between local and systemic analgesia. METHODS: After induction of general anesthesia, 42 patients, aged 1 to 7 yr, scheduled to undergo inguinal hernia repair randomly received a caudal (caudal group) or intramuscular (intramuscular group) injection of 1 mg/kg S(+)-ketamine. Intraoperatively, heart rate (HR), mean arterial pressure (MAP) and arterial oxygen saturation were measured. Postoperative measurements included duration of analgesia, a four-point sedation score, and hemodynamic and respiratory monitoring for 6 h in the recovery room. Analgesic requirements in the recovery room were assessed by an independent blinded observer using an observational pain/discomfort scale (OPS). Plasma samples for determination of ketamine concentrations were obtained before and 10, 20, 30, 45, 60, 90, 120, and 180 min after injection of S(+)-ketamine. RESULTS: A significantly longer duration of analgesia (P < 0.001) was observed after caudal administration (528 min [220-1,440 min]; median [range]) when compared with intramuscular administration (108 min [62-1,440 min]) of S(+)-ketamine. Plasma levels of ketamine were significantly lower from 10 to 45 min after caudal administration than after intramuscular injection. CONCLUSION: Caudal S(+)-ketamine provides good intra- and postoperative analgesia in children. Despite similar plasma concentrations during most of the postoperative observation period, caudal S(+)-ketamine provided more effective analgesia than did intramuscular S(+)-ketamine, indicating a local analgesic effect.     

Long-term intrathecal S(+)-ketamine in a patient with cancer-related neuropathic pain

Neuropathic pain sometimes needs invasive pain therapy. We presentthe case of a patient with cancer-related neuropathic pain untreatablewith conventional pain therapy after tumour-embolization. Thepatient was treated successfully with intrathecal (i.t.) administrationof S(+)-ketamine, in addition to morphine. Plasma concentrationsof S(+)-ketamine were measured regularly throughout the treatment.Continuous i.t. administration of S(+)-ketamine over a periodof 3 months demonstrated low plasma levels and no unwanted side-effects.     

Evaluation of the neuroprotective effects of S(+)-ketamine during open-heart surgery

We compared the effect of S(+)-ketamine to remifentanil, both in combination with propofol, on the neurocognitive outcome after open-heart surgery in 106 patients. A battery of neurocognitive tests was administered before surgery and 1 and 10 wk after surgery. Fourteen patients (25%) in the control group and 10 patients (20%) in the S(+)-ketamine group had 2 or more tests with a cognitive deficit (decline by at least one preoperative SD of that test in all patients) 10 wk after surgery (P = 0.54). Z-scores were calculated for all tests. No significantly better performance could be detected in the S(+)-ketamine group, except for the Trailmaking B test 10 wk after surgery. We conclude that S(+)-ketamine offers no greater neuroprotection compared with remifentanil during open-heart surgery. IMPLICATIONS: N-methyl-D-aspartic acid receptors play an important role during ischemic brain injury. We could not demonstrate that S(+)-ketamine resulted in greater neuroprotective effects compared with remifentanil during cardiopulmonary bypass procedures when both were combined with propofol.     

The synergistic antinociceptive interactions of endomorphin-1 with dexmedetomidine and/or S(+)-ketamine in rats

Spinal administration of the endogenous mu-opioid agonist peptide, endomorphin-1, results in antinociception in rodents, but there are few data about its interaction with other antinociceptive drugs. We investigated the antinociceptive interactions at the spinal level of endomorphin-1 with the N-methyl-D-aspartate antagonist S(+)-ketamine, the alpha2-adrenoceptor agonist dexmedetomidine, or both in awake rats. Nociception was assessed by the tail-flick test. Dose-response curves were determined for endomorphin-1 (0.6-50 microg), for dexmedetomidine (0.1-10 microg), for mixtures of S(+)-ketamine (30 or 100 microg) with endomorphin-1 (2-18 microg) or of endomorphin-1 with dexmedetomidine in a fixed ratio (4:1), and for the triple combination of the three drugs after intrathecal administration. Endomorphin-1 and dexmedetomidine both produced dose-dependent antinociception. The coadministration of 100 microg S(+)-ketamine significantly enhanced the antinociceptive effect of 6 microg endomorphin-1. Isobolographic analysis of the combinations of endomorphin-1 and dexmedetomidine revealed a synergistic interaction between these drugs. The 80% effective dose for the triple combination was significantly less than that for either binary combination. These data indicate that S(+)-ketamine and dexmedetomidine, acting via different receptors, produce synergistic antinociceptive interaction with endomorphin-1 at the spinal level. Furthermore, the triple combination of an opioid agonist, an alpha2-adrenoceptor agonist, and an N-methyl-D-aspartate receptor antagonist shows potent antinociceptive activity. IMPLICATIONS: The coadministration of the N-methyl-D-aspartate antagonist receptor antagonist, S(+)-ketamine, or the specific alpha2-adrenoceptor agonist, dexmedetomidine, significantly enhances the antinociceptive effect of the endogenous mu-opioid agonist, endomorphin-1, at the spinal level. The triple combination of the three drugs causes a further improved antinociception.     

Caudal additives for postoperative pain management in children: S(+)-ketamine and neostigmine

BACKGROUND: The aim of the present pilot study was to compare the analgesic efficacy of S(+)-ketamine either alone or in combination with neostigmine for caudal blockade in pediatric surgery. METHODS: A total of 40 children were randomly assigned to receive after induction of general anesthesia either caudal S(+)-ketamine 1 mg.kg(-1) (group K, n = 20) or caudal S (+)-ketamine 0.5 mg.kg(-1) plus neostigmine 10 microg.kg(-1) (group KN, n = 20). Anesthesia was maintained with sevoflurane and a laryngeal mask airway (LMA), no additional analgesics were administered. Postoperative pain and sedation were assessed by the Children's Hospital of Eastern Ontario Pain Score and Ramsay scale for 24 h. RESULTS: No statistical difference in duration of analgesia and sedation was found. Mean duration of postoperative analgesia was 18 +/- 9.4 h in group K and 21.8 +/- 6.7 h in group KN. There was a significantly higher incidence of postoperative vomiting after administration of caudal ketamine with neostigmine (30% group KN Vs 0% group K; P < 0.05). CONCLUSIONS: This pilot study demonstrates equianalgesic effects on postoperative pain relief in children with both caudal S(+)-ketamine 1 mg.kg(-1) and caudal S(+)-ketamine 0.5 mg.kg(-1) plus neostigmine 10 microg.kg(-1). Further studies are required to confirm adoption of caudal neostigmine into routine clinical practice.     

S(+)-ketamine for long-term sedation in a child with retinoblastoma undergoing interstitial brachytherapy

We report the case of a 14-month-old child undergoing hourly pulse dose radiation therapy (interstitial brachytherapy) for 72 h in whom we employed S(+)-ketamine for sedation during spontaneous breathing.