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.     

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.     

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.     

High-dose S(+)- ketamine improves neurological outcome following incomplete cerebral ischemia in rats

PURPOSE: To determine the effects of the non-competitive NMDA-receptor antagonist S(+)-ketamine on neurological outcome in a rat model of incomplete cerebral ischemia. METHODS: Thirty rats were anesthetized, intubated and mechanically ventilated with isoflurane, O2 30% and nitrous oxide 70%. Following surgery animals were randomly assigned to one of the following treatment groups: Rats in group 1 (n = 10,OFF control) received fentanyl (bolus: 10 microg x kg(-1) i.v.; infusion 25 microg x kg(-1) x h(-1)) and N2O 70% / O2. Rats in group 2 (n = 10) received O2 30% in air and low-dose S(+)-ketamine (infusion: 0.25 mg x kg(-1) x min(-1)). Rats in group 3 (n = 10) received O2 30% in air and high-dose S(+)-ketamine (infusion: 1.0 mg x kg(-1) min(-1)). Following 30 min equilibration period ischemia was induced by combined unilateral common carotid artery ligation and hemorrhagic hypotension to 35 mm Hg for 30 min. Plasma catecholamines were assayed before and at the end of ischemia. Neurological deficit was evaluated for three postischemic days. RESULTS: Neurological outcome was improved with high-dose S(+)-ketamine when compared to fentanyl / N2O -anesthetized controls (9 vs. 1 stroke related deaths, P<0.05). Increases in plasma catecholamine concentrations were higher in fentanyl / N2O -anesthetized (adrenaline baseline 105.5+/-92.1 pg x ml(-1), during ischemia 948+/-602.8 pg x ml(-1), P<0.05; noradrenaline baseline 407+/-120.2 pg x ml(-1), ischemia 1267+/-422.2 pg x ml(-1), P <0.05) than in high-dose S(+)-ketamine-treated animals (adrenaline baseline 71+/-79.5 pg x ml(-1), ischemia 237 +/-131.9; noradrenaline baseline 317.9+/-310.5 pg x ml(-1), ischemia 310.5+/-85.7 pg x ml(-1)). CONCLUSION: Neurological outcome is improved following incomplete cerebral ischemia with S(+)-ketamine. Decreases in neuronal injury may be related to suppression of sympathetic discharge.     

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 effect of hypernatremia on liver allografts in rats

We performed a prospective randomized double-blinded study to test preservative-free S(+)-ketamine alone or in combination with clonidine for intra- and postoperative caudal blockade in pediatric surgery over a 24-h period. Fifty-three children (1-72 mo) scheduled for inguinal hernia repair were caudally injected with either S(+)-ketamine 1 mg/kg alone (Group K) or with additional clonidine (Group C1 = 1 microg/kg; Group C2 = 2 microg/kg) during sevoflurane anesthesia via a laryngeal mask. Intraoperative monitoring included heart rate, blood pressure, and pulse oximetry; postoperative monitoring included a pain discomfort scale and a sedation score. No additional analgesic drugs were required during surgery. The mean duration of postoperative analgesia was 13.3 +/- 9.2 h in Group K, 22.7 +/- 3.5 h in Group C1, and 21.8 +/- 5.2 h in Group C2 (P < 0.0001, Group K versus other groups). Groups C1 and C2 received significantly fewer analgesics in the postoperative period than Group K (15% and 18% vs 63%; P < 0.01). The three groups had similar postoperative sedation scores. We conclude that the combination of S(+)-ketamine 1 mg/kg with clonidine 1 or 2 microg/kg for caudal blockade in children provides excellent analgesia without side effects over a 24-h period. IMPLICATIONS: Caudally administered preservative-free S(+)-ketamine combined with 1 or 2 microg/kg clonidine provides excellent perioperative analgesia in children and has minimal side effects.     

Ketamine and midazolam is an inappropriate preinduction combination in uncooperative children undergoing brief ambulatory procedures

BACKGROUND: We prospectively studied the effects of intramuscular (i.m.) ketamine alone, or combined with midazolam, on mask acceptance and recovery in young children who were uncooperative during induction of anaesthesia. METHODS: The Institutional Review Board (IRB) approval was obtained to study 80 children, 1-3 years, scheduled for bilateral myringotomies and tube insertion (BMT). Mask induction was attempted in all the children. Those who were uncooperative were randomly assigned to one of the four preinduction treatment groups: group I, ketamine 2 mg.kg(-1); group II, ketamine 2 mg.kg(-1) combined with midazolam 0.1 mg.kg(-1); group III, ketamine 2 mg.kg(-1) with midazolam 0.2 mg.kg(-1); or group IV, ketamine 1 mg.kg(-1) with midazolam 0.2 mg.kg(-1). Anaesthesia was continued with nitrous oxide and halothane by facemask. RESULTS: Children in all treatment groups achieved satisfactory sedation in less than 3 min following the administration of the preinduction drug(s). Compared with patients who received halothane induction (comparison group), the use of ketamine alone did not significantly (P > 0.0167, a Bonferroni corrected significance level) delay recovery and discharge times (18.8 +/- 2.5 and 82.5 +/- 30.7 min vs 12.6 +/- 4.6 and 81.0 +/- 33.8 min, P = 0.030 and P = 0.941, respectively). Patients who received ketamine/midazolam combinations, however, had significantly longer recovery and discharge times vs halothane (32.3 +/- 14.0 and 128.0 +/- 36.6 min, P = 0.001, P = 0.007, respectively). These times were so clinically unacceptable, that the study had to be terminated with only 17 patients receiving study drugs. CONCLUSIONS: It is concluded that ketamine/midazolam combination is not appropriate for preinduction of anaesthesia in paediatric ambulatory patients because of unacceptably prolonged recovery and delayed discharge times.     

A comparison of dexmedetomidine and midazolam for sedation in third molar surgery

This randomised, double-blind study compared dexmedetomidine and midazolam for intravenous sedation during third molar surgery under local anaesthesia. Sixty patients received either dexmedetomidine (up to 1 microg x kg(-1)) or midazolam (up to 5 mg), which was infused until the Ramsay Sedation Score was four or the maximum dose limit was reached. Intra-operative vital signs, postoperative pain scores and analgesic consumption, amnesia, and satisfaction scores for patients and surgeons, were recorded. Sedation was achieved by median (IQR (range)) doses of 47 microg (39-52 (25-76)) or 0.88 microg x kg(-1) (0.75-1.0 (0.6-1.0)) dexmedetomidine, and 3.6 mg (3.3-4.4 (1.9-5.0)) or 0.07 mg x kg(-1) (0.055-0.085 (0.017-0.12)) midazolam. Heart rate and blood pressure during surgery were lower in dexmedetomidine group. There was no significant difference in satisfaction or pain scores. Midazolam was associated with greater amnesia. Dexmedetomidine produces comparable sedation to midazolam.     

Rescue sedation with dexmedetomidine for diagnostic imaging: a preliminary report

BACKGROUND: Sedation is frequently required during noninvasive radiological imaging in children. Although commonly used agents such as chloral hydrate and midazolam are generally effective, failures may occur. The authors report their experience with dexmedetomidine for rescue sedation during magnetic resonance imaging. METHODS: A retrospective chart review was undertaken. RESULTS: The cohort included five patients ranging in age from 11 months to 16 years. Following the failure of other agents (chloral hydrate and/or midazolam), dexmedetomidine was administered as a loading dose of 0.3-1.0 microg x kg(-1) x min(-1) over 5-10 min followed by an infusion of 0.5-1.0 microg x kg(-1) x h(-1). The dexmedetomidine loading dose required to induce sedation was 0.78 +/- 0.42 microg x kg(-1) (range 0.3-1.2). The maintenance infusion rate was 0.57 +/- 0.06 microg x kg(-1) x h(-1) (range 0.48-0.69). The imaging procedures were completed without difficulty. No patient required additional bolus administrations or changes in the infusion rate. The duration of the dexmedetomidine infusion ranged from 30 to 50 min. The mean decrease in heart rate was 13.6 +/- 5.1 b x min(-1) (14.3 +/- 5.0% from baseline; P = 0.02), the mean decrease in systolic blood pressure was 26.4 +/- 15.2 mmHg (24.6 +/- 12.4% decrease from baseline; P = 0.004), and the mean decrease in respiratory rate was 1.4 +/- 1.5 min(-1) (7.5 +/- 7.9% decrease from baseline; P = NS). P(E)CO2 exceeded 6.5 kPa (50 mmHg) in one patient [maximum 6.6 kPa (51 mmHg)] with a maximum value of 6.0 +/- 0.4 kPa (46 +/- 3 mmHg). Oxygen saturation decreased from 98 +/- 1 to 95 +/- 1%; P = 0.001. No patient developed hypoxemia (oxygen saturation less than 90%). Mean time to recovery to baseline status was 112.5 +/- 50.6 min and time to discharge was 173.8 +/- 83.8 min. CONCLUSIONS: Our preliminary experience suggests that dexmedetomidine may be an effective agent for procedural sedation during radiological imaging. Its potential application in this setting is discussed and other reports regarding its use in pediatric patients are reviewed.     

Remifentanil versus morphine analgesia and sedation for mechanically ventilated critically ill patients: a randomized double blind study

BACKGROUND: The rapid onset and offset of action of remifentanil could make it quickly adjustable to the required level of sedation in critically ill patients. The authors hypothesized that the efficacy of a remifentanil-based regimen was greater than that of a morphine-based regimen. METHODS: Forty intent-to-treat patients were randomly allocated to receive a blinded infusion of either remifentanil 0.15 microg x kg(-1) x min(-1) or morphine 0.75 microg x kg(-1) x min(-1). The opioid infusion was titrated, in the first intent, to achieve optimal sedation defined as Sedation Agitation scale of 4. A midazolam open-label infusion was started if additional sedation was required. RESULTS: The mean percentage hours of optimal sedation was significantly longer in the remifentanil group (78.3 +/- 6.2) than in the morphine group (66.5 +/- 8.5). This was achieved with less frequent infusion rate adjustments (0.34 +/- 0.25 changes/h) than in the morphine group (0.42 +/- 0.22 changes/h). The mean duration of mechanical ventilation and extubation time were significantly longer in the morphine group (18.1 +/- 3.4 h, 73 +/- 7 min) than in the remifentanil group (14.1 +/- 2.8 h, 17 +/- 6 min), respectively. Remifentanil mean infusion rate was 0.13 +/- 0.03 microg x kg(-1) x min(-1), whereas morphine mean infusion rate was 0.68 +/- 0.28 microg x kg(-1) x min(-1). More subjects in the morphine group (9 of 20) than in the remifentanil group (6 of 20) required midazolam. The incidence of adverse events was low and comparable across the two treatment groups. CONCLUSIONS: A remifentanil-based regimen was more effective in the provision of optimal analgesia-sedation than a standard morphine-based regimen. The remifentanil-based regimen allowed a more rapid emergence from sedation and facilitated earlier extubation.     

Clonidine vs. midazolam as premedication in children undergoing adeno-tonsillectomy: a prospective, randomized, controlled clinical trial

BACKGROUND: Clonidine administration in the setting of paediatric anaesthesia is associated with a number of desirable effects, e.g. preoperative sedation, analgesia and reduced anaesthetic requirements. The aim of the current study was to compare postoperative outcome variables using a prospective, randomized, double-blind design after premedication with clonidine or midazolam. METHODS: One hundred paediatric ASA physical status 1 patients (age 1-11 year) scheduled for adeno-tonsillectomy were assigned to receive rectal premedication with midazolam (300 microg kg(-1) and atropine 40 microg kg(-1); group M, n = 52) or clonidine (5 microg kg(-1 and) atropine 40 microg kg(-1); group C, n = 48) prior to a standardized sevoflurane anaesthetic. The incidence of immediate postoperative pain (0-2 h), as assessed by repeated Objective Pain Scale (OPS) scores, was chosen as the primary end-point of the study. Degree of sedation (modified Vancouver sedation scale 0-3), occurrence of postoperative vomiting (POV), and incidence of shivering and immediate postoperative confusion were registered as secondary end-points. After hospital discharge parents were instructed to continue the evaluation of pain, sedation, POV and sleep pattern during a 24-h period. Parents were also asked for their preference concerning the postoperative behaviour of their child (calm, sedated vs. alert, active). RESULTS: In the early postoperative period patients in the clonidine group had a significantly lower sum of 5 OPS scores (median = 8.0) compared to group M (median = 11.5) (P = 0.011). Administration of clonidine was also associated with a slightly higher sum of sedation scores (median = 13) in the early postoperative period compared to children receiving midazolam (median = 12) (P < 0.001). No episode of shivering was observed in the clonidine group but was present in five of the patients in the midazolam group (P = 0.057). In younger children (< 5 years) the incidence of postoperative confusion was lower in the clonidine group (P = 0.001). No difference in the frequencies of POV incidences, degree of postoperative pain, need for analgesics, or sleep pattern during the first 24 postoperative hours could be observed between the groups according to the parental evaluation. Children premedicated with clonidine were more calm and sedated compared to children in the midazolam group (P = 0.024) as judged by their parents. A significant majority of parents (75%; P < 0.001) preferred a calm and sedated child during the first postoperative 24-h period. CONCLUSION: Rectal premedication with clonidine was associated with a significant reduction of pain in the early postoperative period compared to midazolam and was also associated with moderately increased sedation during the first 24 postoperative hours. The sedative effect of clonidine is in agreement with the unambiguous finding of a parental preference for a calm and sedated child during the first 24 postoperative hours.     

Caudal neostigmine for postoperative analgesia in paediatric surgery

BACKGROUND: This study was conducted to evaluate analgesia and side-effects of caudal neostigmine coadministered with bupivacaine in paediatric surgery. METHODS: We studied children, aged 1-5 years, undergoing elective surgery (inguinal hernia and hypospadias). After standard induction of anaesthesia, caudal anaesthesia was performed. Group 1 received 0.25% bupivacaine 0.5 ml.kg-1 and Group 2 received 0.25% bupivacaine 0.5 ml x kg-1 with 1 microg x kg-1 neostigmine via the caudal route. Heart rate, mean arterial pressure, peripheral oxygen saturation were recorded before induction, after induction but before caudal anaesthesia, and then every 5 min after caudal anaesthesia. Haemodynamic, Toddler, Preschooler, Postoperative Pain Scale (TPPPS) pain score and sedation score values were recorded 30 min after extubation and at hours 2, 4, 6, 12 and 24. A pain score >3/10 resulted in administration of rectal paracetamol. The duration of postoperative analgesia was defined as the time between caudal drug injection and the first rectal paracetamol administration. RESULTS: There were no differences between the groups in demographic and haemodynamic date, duration of surgery and anaesthesia, time to extubation or sedation scores. The duration of postoperative pain relief did not differ between the two groups; 15.40 +/- 10.97 h for group 1 vs. 15.45 +/- 10.99 h for group 2 (P > 0.05). The incidence of nausea (three patients in group 2 and one patient in group 1) was not statistically significant. No other side-effects were seen. CONCLUSIONS: We found that a single caudal injection of 1 microg x kg-1 neostigmine mixed with bupivacaine offers no significant advantage over bupivacaine alone for postoperative pain relief in children undergoing genitourinary surgery.     

The use of midazolam and small-dose ketamine for sedation and analgesia during local anesthesia.

Small-dose ketamine in combination with sedative drugs has increasingly been used for sedation and analgesia in local anesthesia. We compared the clinical efficacy of midazolam with two different ketamine infusion regimens during plastic surgery under local anesthesia. Sixty patients undergoing plastic surgery procedures with local anesthesia were randomly assigned to two groups of 30 patients each in a double-blinded fashion. All patients received a bolus of 0.05 mg/kg midazolam, followed by a stepwise infusion: 1.67 microg x kg(-1) x min(-1) for the first 30 min, then reduced to 1.33 microg x kg(-1) x min(-1) for 90 min and subsequently to 1 microg x kg(-1) x min(-1). Two minutes before the infiltration of local anesthetic solution, a bolus of ketamine 0.3 mg/kg IV was administered, followed by a stepwise infusion of ketamine: Group A, 16.67 microg x kg(-1) x min(-1) for 30 min, 13.3 microg x kg(-1) x min(-1) for 90 min, and subsequently 10 microg x kg(-1) x min(-1); Group B, 8.33 microg x kg(-1) x min(-1) for 30 min, 6.67 microg x kg(-1) x min(-1) for 90 min, and then 5 microg x kg(-1) x min(-1). The level of sedation was evaluated by using the modified Observer's Assessment of Alertness/Sedation scale. We observed the effects of the two ketamine infusion regimens on sedation levels, respiratory and cardiovascular variables, and perioperative side effects. In both groups, midazolam and ketamine produced adequate sedation (with Observer's Assessment of Alertness/Sedation scores of 2-4) without significant respiratory and cardiovascular depression during surgery. However, there were fewer disruptive movements and there was less postoperative vomiting in Group B (P < 0.01). In conclusion, ketamine and midazolam provided satisfactory intraoperative sedation, analgesia, and amnesia in both groups. However, side effects associated with ketamine occurred less often in the smaller-dose ketamine group. IMPLICATIONS: Sedation and analgesia are often provided during local anesthesia. This study demonstrates that a small-dose ketamine infusion in combination with midazolam provided satisfactory intraoperative sedation, analgesia, and amnesia in healthy plastic-surgery patients when it was used to supplement local anesthesia.     

Perioperative small-dose S(+)-ketamine has no incremental beneficial effects on postoperative pain when standard-practice opioid infusions are used

Several studies report that when small-dose racemic ketamine, an N-methyl-D-aspartate receptor antagonist, is administered perioperatively, opioid consumption is reduced postoperatively. S(+)-ketamine has a higher affinity for the N-methyl-D-aspartate receptor and less-serious side effects than racemic ketamine. Thirty patients scheduled for elective arthroscopic anterior cruciate ligament repair were enrolled in this randomized, double-blinded clinical trial designed to determine the preemptive effect of S(+)-ketamine on postoperative analgesia requirements in a setting of clinically relevant perioperative analgesia. Total IV anesthesia was induced and maintained with remifentanil (0.125-1.0 microg x kg(-1) x min(-1)) and a propofol target-controlled infusion (target 2-4 microg/mL). The Ketamine group received a bolus of 0.5 mg/kg S(+)-ketamine before incision, followed by a continuing infusion of 2 microg x kg(-1) x min(-1) until 2 h after emergence from anesthesia. The Control group received NaCl in the same sequence. After IV morphine provided pain relief down to < or =3 on a visual analog scale scored from 0 to 10, patients were connected to a patient-controlled analgesia device. There were no significant differences between the two groups in terms of total morphine consumption or VAS scores, either at rest or with movement. In our study, S(+)-ketamine did not contribute to postoperative pain reduction, possibly because of the clinically routine perioperative opioid analgesia. IMPLICATIONS: Small-dose S(+)-ketamine had no positive effect on postoperative analgesia when administered perioperatively for elective arthroscopic anterior cruciate ligament repair. Unlike investigations of the racemic mixture of ketamine, our study methods included timely standard-practice perioperative opioid analgesia, which seems to make supplemental analgesia unnecessary.     

S(+)-ketamine as an analgesic adjunct reduces opioid consumption after cardiac surgery

There are no studies evaluating S(+)-ketamine for pain management after sternotomy. In this prospective, randomized, double-blind, placebo-controlled clinical trial, we evaluated the efficacy and feasibility of S(+)-ketamine as an adjunctive analgesic after cardiac surgery. Ninety patients scheduled for elective coronary artery bypass grafting (CABG) were randomized to receive either a 75 microg/kg bolus of S(+)-ketamine followed by a continuous infusion of 1.25 microg . kg(-1) . min(-1) for 48 h (n = 44) or placebo (normal saline bolus and infusion) (n = 46). From the time of tracheal extubation, patients could access an opioid (oxycodone) via a patient-controlled analgesia device, and the cumulative oxycodone doses were measured over 48 h. Pain was evaluated on a visual analog scale three times daily. The quality of recovery, patient satisfaction with pain management, and adverse effects were recorded. The cumulative oxycodone consumption during the first 48 postoperative hours was less in the S(+)-ketamine group (103 +/- 44 mg) than in the placebo group (125 +/- 45 mg; mean difference, 22 mg; 95% confidence interval for the difference, 3-40 mg; P = 0.023). Pain scores did not differ between the groups at rest (P = 0.17) or during a deep breath (P = 0.23). Patient satisfaction was superior in S(+)-ketamine-treated patients: 26 (60%) of 44 in the S(+)-ketamine group compared with 16 (35%) of 46 in the placebo group were very satisfied with the analgesic management (P = 0.032). Nausea and vomiting were the most common adverse events, with similar frequencies in both groups. Four patients in the S(+)-ketamine group developed transient hallucinations during the infusion, versus none in the placebo group. In conclusion, small-dose S(+)-ketamine decreased opioid consumption in CABG patients during the first 48 h after surgery.     

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.      

Experience in postoperative sedation with dexmedetomidine for mandibular osteotomy

BACKGROUND: Dexmedetomidine may be suitable for postoperative sedation of patients with mandibular osteotomy. METHODS: Twenty patients were sedated with dexmedetomidine (group D) employing loading infusion at 1.0 microg x kg(-) x hr(-1) and then continuous infusion at 0.7 mg x kg(-1) x hr(-1). Other twenty patients were sedated with midazolam 0.1 mg x kg(-1) (group C). Ramsay score was recorded at 3 hours and 12 hours after infusing sedative drugs. Then, we questioned patients, nurses and doctors. RESULTS: Ramsay score in the group D was higher than that in the group C (P < 0.01). Hypotension and respiratory depression did not occur. But bradycardia occurred in two cases. By adding propofol, group D showed more effective sedation. CONCLUSIONS: This study shows that sedation with dexmedetomidine is more suitable than that with midazolam.     

Remifentanil-Propofol- versus Fentanyl-Midazolam-Kombination bei intrakraniellen Eingriffen

INTRODUCTION: After neurosurgery patients often need to be sedated and ventilated in the intensive care unit (ICU). However, rapid postoperative recovery and neurological examination are particularly important for the early recognition of complications. In this retrospective study two different strategies of anaesthesia technique and ICU sedation (fentanyl-midazolam versus remifentanil-propofol) were compared. METHODS: Intraoperatively, patients received continuous infusions of either fentanyl (0.2-1.0 mg/h) and midazolam (2-10 mg/h) or remifentanil (0.2-0.5 microg/kg body weight/min) and propofol (3-6 mg/kg body weight/h). After arrival in the ICU fentanyl (0.03-0.2 mg/h) and midazolam (2-12 mg/h) or remifentanil (0.1-0.2 microg/kg body weight/min) and propofol (0.5-3 mg/kg body weight/h) were infused to reach a Ramsay score of 4. The times between termination of infusion and extubation and the length of stay in the ICU were examined. RESULTS: A total of 60 patients (n=30 each group) undergoing supratentorial brain tumour surgery were enrolled. The groups were comparable for age, weight, ASA status (American Society of Anesthesiologists) and duration of drug administration (remifentanil-propofol 528+/-382 min versus fentanyl-midazolam 548+/-360 min). Extubation times were significantly shorter after remifentanil-propofol (47 min) than after fentanyl-midazolam (481 min), and the length of stay in the ICU was also significantly reduced (1.8 days versus 3.7 days). As a result of prolonged unconsciousness and impaired neurological assessability, a brain CT scan was necessary in 3 patients after fentanyl-midazolam to exclude neurosurgical complications. CONCLUSION: This retrospective study demonstrates that remifentanil-propofol anaesthesia and ICU sedation are superior to the combination of fentanyl and midazolam in terms of ventilation time and length of ICU stay. Moreover, the use of fentanyl-midazolam may lead to unnecessary CT scans.     

Oral sedation with midazolam and diphenhydramine compared with midazolam alone in children undergoing magnetic resonance imaging

BACKGROUND: The purpose of this study was to compare the safety and efficacy of oral midazolam and midazolam-diphenhydramine combination to sedate children undergoing magnetic resonance imaging (MRI). METHODS: We performed a prospective randomized double-blind study in 96 children who were randomly allocated into two groups. Group D received oral diphenhydramine (1.25 mg x kg(-1)) with midazolam (0.5 mg x kg(-1)), and Group P received oral placebo with midazolam (0.5 mg x kg(-1)) alone. Sedation scores, onset and duration of sleep were evaluated. Adverse effects, including hypoxemia, failed sedation, and the return of baseline activity, were documented. RESULTS: Diphenhydramine facilitated an earlier onset of midazolam sedation (P < 0.01), and higher sedation scores (P < 0.01). In children who received midazolam alone, 20 (41%) were inadequately sedated, compared with 9 (18%) children who received midazolam and diphenhydramine combination (P < 0.01). Time to complete recovery was not significantly different between the two groups. CONCLUSIONS: Our study indicates that the combination of oral diphenhydramine with oral midazolam resulted in safe and effective sedation for children undergoing MRI. The use of this combination might be more advantageous compared with midazolam alone, resulting in less sedation failure during MRI.