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.     

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.     

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.      

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.     

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.     

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.     

The comparison of caudal ketamine,alfentanil and ketamine plus alfentanil administration for postoperative analgesia in children

BACKGROUND: Our aim was to compare the effect of single dose caudal ketamine, alfentanil or a mixture of both drugs in the treatment of pain after hypospadias repair surgery in children. METHODS: The group comprised 109 boys, ASA I-II, aged 1-9 years, who were undergoing hypospadias repair surgery as day cases. The children were randomly divided into three groups for postoperative analgesia: group 1, only alfentanil (20 microg x kg(-10) was given caudally; group 2, ketamine (0.5 mg x kg(-1)) alone; and group 3, alfentanil (20 microg x kg(-1))-ketamine (0.5 mg x kg(-1)) was given caudally. The analgesic effect of caudal block was evaluated using the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) and sedation was assessed using a five-point sedation score. The first analgesic requirement time and the number of supplementary analgesics required by each child in a 24-h period were also recorded. RESULTS: No statistical differences were found in demographic characteristics, haemodynamic and respiratory parameters, objective pain scores, postoperative sedation scores and duration of surgery among the groups. The median time to first analgesia was significantly shorter in group 1 than in groups 2 and 3 (P=0.009, P=0.001). Significantly more patients in group 1 required additional postoperative analgesia (paracetamol 15 mg x kg(-1)) compared with groups 2 and 3 (P < 0.001). CONCLUSIONS: Caudal administration of ketamine 0.5 mg.kg-1 with or without alfentanil in children produced satisfactory postoperative analgesia without respiratory depression or other side-effects.     

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.     

Analgesic effectiveness of caudal levobupivacaine and ketamine

Background: Ketamine is used increasingly in paediatric anaesthetic practiceto prolong the action of a caudal block. This study was designedto determine if adding S(+)-ketamine 0.5 mg kg^–1 allowsa lower concentration of levobupivacaine to be used for caudalanaesthesia without loss of clinical effectiveness. Methods: One hundred and sixty-four children (ASA I or II) aged 3 months–6yr were randomly allocated to receive 1 ml kg^–1 of levobupivacaine0.15% with 0.5 mg kg^–1 S(+)-ketamine (Group 1), levobupivacaine0.175% with 0.5 mg kg^–1 S(+)-ketamine (Group 2), or levobupivacaine0.2% (Group 3) by the caudal route. Pain, motor block, sedation,and requirement for postoperative analgesia were assessed upto 6 h after operation. Results: There was no significant difference between the groups in effectivenessat first surgical incision. Significantly lower analgesic requirementswere reported in Group 2 compared with Group 3 at wakeup, 180and 360 min after operation. Time to first rescue analgesiawas longer in Group 2 compared with Group 1 or 3. Kaplan–Meiersurvival analysis of analgesia free time demonstrated a significantadvantage of Group 2 over Groups 1 and 3 (log rank P=0.05).The incidence of postoperative motor block was not significantlydifferent between the groups. No excess sedation or dysphoricreactions were observed in the ketamine groups. Conclusions: The addition of 0.5 mg kg^–1 S(+)-ketamine to levobupivacaine0.175% for caudal analgesia for lower abdominal and urologicalsurgery is significantly more effective in providing postoperativeanalgesia than levobupivacaine 0.15% with 0.5 mg kg^–1S(+)-ketamine or levobupivacaine 0.2%.     

The combination of epidural clonidine and S(+)-ketamine did not enhance analgesic efficacy beyond that for each individual drug in adult orthopedic surgery

STUDY OBJECTIVES: To evaluate the benefit of epidural clonidine and S(+)-ketamine combination through the epidural route in adult orthopedic surgery. DESIGN: Randomized double-blinded study. SETTING: Teaching hospital. PATIENTS: Scheduled to undergo knee surgery, 56 American Society of Anesthesiologists physical status 1 and 2 adult patients. INTERVENTIONS: Patients were randomized to 1 of 4 groups to receive the combined epidural-intrathecal technique. A 10-mL epidural injection of either study drug or normal saline was first administered to all patients. Intrathecal anesthesia was performed with 15 mg of bupivacaine. The control group (CG) received epidural saline. The 0.1-mg/kg S(+)-ketamine epidural group received 0.1 mg/kg epidural S(+)-ketamine. The 0.5-microg/kg clonidine epidural group received 0.5 microg/kg epidural clonidine. The S(+)-ketamine/clonidine group received 0.1 mg/kg epidural S(+)-ketamine plus 0.5 microg/kg epidural clonidine. MEASUREMENTS AND MAIN RESULTS: Pain and adverse effects were evaluated by visual analog scale. Rescue analgesics were available to patients. The groups were demographically similar. Sensory level to pinprick, surgical and anesthetic time, and visual analog scale scores for pain at first rescue medication were similar among the groups. The time to first rescue analgesic (minute) was lowest in CG (P < .005). The CG required more rescue analgesics in 24 hours than any of the other groups (P < .0005). Patients who received either epidural clonidine, S(+)-ketamine, or both displayed similar analgesia. The frequency of adverse effects was similar among groups (P > .05). CONCLUSIONS: The association of epidural clonidine or S(+)-ketamine did not result in a greater analgesic effect in the model of acute postoperative pain studied, although the interaction of epidural clonidine and S(+)-ketamine is not attributable to sharing of a common second messenger system.     

A randomised, controlled study of peri-operative low dose s(+)-ketamine in combination with postoperative patient-controlled s(+)-ketamine and morphine after radical prostatectomy

In a randomised, double-blind prospective study we compared the effects on postoperative pain and analgesic consumption of intra-operative s(+)-ketamine (100 microg.kg-1 bolus and a continuous infusion of 2 microg.kg-1.min-1) followed by postoperative patient-controlled analgesia with morphine (1 mg per bolus) plus s(+)-ketamine (0.5 mg per bolus), or intra-operative saline followed by postoperative patient-controlled analgesia morphine (1 mg per bolus) alone. A total of 28 male patients undergoing radical prostatectomy were studied. Morphine consumption, pain scores, pressure algometry and adverse effects were recorded for 48 h after surgery. Cumulative morphine consumption was significantly lower in the ketamine/morphine group (47.9 +/- 26.2 mg) than in the saline/morphine group (73.4 +/- 34.8 mg; p = 0.049). Pain scores at rest were significantly lower in the ketamine/morphine group across the 48-h study period (p = 0.01). No significant differences were found in pressure algometry measurements or the occurrence of adverse effects.     

Anaesthesia with midazolam and S-(+)-ketamine in spontaneously breathing paediatric patients during magnetic resonance imaging

We evaluated safety and efficacy of a sedation technique based on rectal and intravenous S-(+)-ketamine and midazolam to achieve immobilization during Magnetic Resonance Imaging (MRI). Thirty-four paediatric patients were randomly assigned to undergo either the sedation protocol (study group) or general anaesthesia (control group). Imaging was successfully completed in all children. Children in the study group received a rectal bolus (0.5 mg x kg(-1) midazolam and 5 mg x kg(-1) S-(+)-ketamine) and required additional i.v. supplementation (20+/-10 microg x kg(-1) x min(-1) S-(+)-ketamine and 4+/-2 microg x kg(-1) x min(-1) midazolam), spontaneous ventilation was maintained. Transient desaturation occurred once during sedation and four times in the control group (P=0.34). PECO2 was 5.3+/-0.5 kPa (40+/-4 mm Hg) in the study group and 4.1+/-0.6 kPa (31+/-5 mm Hg) in the control group (P<0.001). Induction and discharge times were shorter in the study group (P<0.001), recovery times did not differ significantly between the groups. Our study confirms that a combination of rectal and supplemental intravenous S-(+)-ketamine plus midazolam is a safe and useful alternative to general anaesthesia for MRI in selected paediatric patients.     

Epidural neostigmine produces analgesia but also sedation in women after cesarean delivery

BACKGROUND: Intrathecal neostigmine produces analgesia but also nausea, limiting its utility. In contrast, epidural administration of neostigmine has been suggested to produce postoperative analgesia without nausea in nonpregnant patients. The purpose of this study was to examine the dose range for efficacy and side effects of epidural neostigmine in women at cesarean delivery receiving combined spinal-epidural anesthesia. METHODS: After institutional approval and informed consent, 80 patients for elective cesarean delivery were given combined spinal-epidural anesthesia with 8 mg hyperbaric bupivacaine plus 10 microg fentanyl. Patients were randomized to receive either saline or 75, 150, or 300 microg neostigmine (n = 20 per group) in 10 ml saline after cord clamping. Pain, morphine consumption, and side effects were monitored for 24 h. RESULTS: Global pain assessment for the first 24 h was reduced from 5.4 +/- 0.2 in the saline group to 3.0-3.5 +/- 0.3 in the neostigmine groups, dose independently. Correspondingly, global satisfaction with neostigmine was also improved (P < 0.05). Nausea and morphine consumption were similar among groups. Intraoperative shivering and sedation were increased in the 300-microg neostigmine group only (P < 0.05), and postoperative sedation was increased by neostigmine in a dose-independent fashion (P < 0.05). CONCLUSIONS: Epidural neostigmine produced modest analgesia in women after cesarean delivery. In contrast with previous reports, which focused primarily on nausea, these data suggest that epidural neostigmine can also produce mild sedation for several hours. These data suggest a limited role for single bolus-administration epidural neostigmine for analgesia after cesarean delivery. They also support future study of epidural neostigmine for obstetric analgesia.     

Double-blind randomized controlled trial of caudal versus intravenous S(+)-ketamine for supplementation of caudal analgesia in children

Background. The postoperative analgesic efficacy of S(+)-ketamineafter caudal or i.v. administration following sub-umbilicalsurgery in children was studied to investigate its principalsite of analgesic action. Methods. Sixty children undergoing caudal block during generalanaesthesia for hernia repair or orchidopexy were prospectivelyrandomized to one of three groups: the bupivicaine group receivedplain bupivacaine 0.25% 1 ml kg^–1; the caudal ketaminegroup received caudal plain bupivacaine 0.25% 1 ml kg^–1with S(+)-ketamine 0.5 mg kg^–1; the i.v. ketamine groupreceived caudal plain bupivacaine 0.25% 1 ml kg^–1 plusS(+)-ketamine 0.5 mg kg^–1 i.v.. Postoperative measurementsincluded analgesic requirements and modified objective painscore for the first 24 h. Results. The median time to first analgesia was significantlylonger in the caudal ketamine group (10 h) than in the i.v.ketamine (4.63 h) or bupivacaine (4.75 h) groups (P=0.01). Significantlyfewer doses of analgesia were required over the first postoperative24 h by subjects in the caudal ketamine group (median 1) comparedwith the i.v. ketamine (median 2) or bupivacaine (median 2.5)groups (P<0.05). There was no difference between the groupsin the incidence of postoperative nausea and vomiting or psychomotorreactions. Conclusions. We have demonstrated that the addition of caudalS(+)-ketamine to bupivacaine prolongs the duration of postoperativeanalgesia. However, the same dose of i.v. S(+)-ketamine combinedwith a plain bupivacaine caudal provides no better analgesiathan caudal bupivacaine alone, indicating that the principalanalgesic effect of caudal S(+)-ketamine results from a localneuroaxial rather than a systemic effect. Br J Anaesth 2004; 92: 344–7     

How to prolong postoperative analgesia after caudal anaesthesia with ropivacaine in children: S-ketamine versus clonidine

BACKGROUND: The aim of the study was to determine whether caudal S-ketamine or clonidine prolonged analgesia together with ropivacaine. METHODS: Sixty-three boys, aged 1-5 years, who were undergoing minor surgery, were allocated in order to receive one of three solutions for caudal anaesthesia. Group R received 2 mg x kg(-1) 0.2% ropivacaine; group C, 2 mg x kg(-1) 0.2% ropivacaine + clonidine 2 microg x kg(-1); and group K, 2 mg x kg(-1) 0.2% ropivacaine + S-ketamine 0.5 mg x kg(-1). RESULTS: Postoperative analgesia assessed by CHEOPS lasted 701 min in group K (P < 0.05) compared with 492 min in group C and 291 min in group R. There were no significant differences between the groups for incidence of haemodynamic and respiratory alterations, motor block or sedation. CONCLUSIONS: This study demonstrates that S-ketamine 0.5 mg x kg(-1) when added to 0.2% caudal ropivacaine provides better postoperative analgesia than clonidine without any clinically significant side-effect.     

小儿骶管复合用药对术后镇痛的影响

目的观察小儿骶管复合用药对术后镇痛的影响。方法80例1～4岁患儿随机分为四组,每组20例。在静脉麻醉后行1%利多卡因1ml/kg骶管阻滞:Ⅰ组局麻药中不加其他药,Ⅱ组加芬太尼2μg/kg,Ⅲ组局麻药中加新斯的明2μg/kg,Ⅳ组局麻药中加曲马多2mg/kg。术后给予芬太尼护师控制泵注镇痛(NCA)治疗。分别于术后1、2、4、6、24h观察镇痛和镇静评分,记录镇痛时间(初次NCA)、NCA芬太尼用量、不良反应及出院时间。结果Ⅳ组的镇痛时间(510.7±64.9)min,长于Ⅰ组的(174.5±39.3)min、Ⅱ组的(291.7±50.8)min和Ⅲ组的(242.0±62.8)min(P0.01)。但Ⅳ组术后恶心呕吐的发生率高于其他三组(P0.05)。结论2mg/kg曲马多复合1%利多卡因1ml/kg行小儿骶管阻滞的术后镇痛效果较好,但其恶心呕吐发生率也有所增加。     

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.     

Small-dose S(+)-ketamine reduces postoperative pain when applied with ropivacaine in epidural anesthesia for total knee arthroplasty

Reduction of nociceptive input through blockade of N-methyl-D-aspartate (NMDA) receptors has been reported. We compared the effects of epidural S(+)-ketamine versus placebo on postoperative pain in a randomized, double-blinded study in 37 patients undergoing unilateral knee arthroplasty. After lumbar epidural anesthesia with ropivacaine (10 mg/mL, 10-20 mL), 19 patients received 0.9% epidural saline, and 18 patients received 0.25 mg/kg epidural S(+)-ketamine 10 min before surgical incision. After surgery, patient-controlled epidural analgesia with ropivacaine was provided. During the first 8 h after surgery, visual analog scale pain rating was similar between groups. Twenty-four and 48 h after surgery, patients anesthetized with ropivacaine had higher visual analog scale ratings at rest and during movement (P < 0.05) than patients anesthetized with S(+)-ketamine and ropivacaine. Forty-eight hours after surgery, patients anesthetized with ropivacaine also consumed more ropivacaine (558 +/- 210 mg) (P < 0.01) than those anesthetized with S(+)-ketamine and ropivacaine (319 +/- 204 mg). Adverse events were similar between groups. Patients who received S(+)-ketamine and ropivacaine rated the quality of their pain therapy better than those who received ropivacaine alone (P < 0.05). We conclude that the combination of S(+)-ketamine and ropivacaine in epidural anesthesia increases postoperative pain relief when compared with ropivacaine. IMPLICATIONS: Epidural S(+)-ketamine applied with ropivacaine before surgery is a rational approach to decrease injury-induced pain sensitization. Epidural blockade with an N-methyl-D-aspartate receptor antagonist and a local anesthetic may provide better analgesia in the postoperative period than a local anesthetic alone.     

The Effect of Transdermal Nitroglycerin on Spinal S(+)-Ketamine Antinociception Following Orthopedic Surgery

STUDY OBJECTIVES: To determine whether combination of transdermal nitroglycerine (a nitric oxide generator) would enhance analgesia from epidural S(+)-ketamine (a N-methyl-D-aspartate antagonist) in patients undergoing orthopedic surgery with combined spinal anesthesia. DESIGN: Randomized, double-blind study. SETTING: Orthopedic surgery unit of a teaching hospital. PATIENTS: 60 ASA physical status I and II patients scheduled for minor orthopedic knee surgery. INTERVENTIONS: Patients were randomized to one of five groups (n = 12) to receive combined epidural/intrathecal anesthesia. A 10-mL epidural injection was first administered to all patients (study drug or normal saline). Intrathecal anesthesia consisted of 15 mg bupivacaine. Twenty to 30 minutes after the spinal puncture, a transdermal patch of either nitroglycerin 5 mg or placebo was applied. The control group (CG) received epidural saline and transdermal placebo. The nitroglycerin group (NG) received epidural saline and transdermal nitroglycerine patch. The 0.1 mg/kg S(+)-ketamine epidural group (1 KG) received 0.1 mg/kg epidural S(+)-ketamine and transdermal placebo. The 0.2 mg/kg S(+)-ketamine epidural group (2 KG) received 0.2 mg/kg epidural S(+)-ketamine and transdermal placebo. Finally, the nitroglycerin/0.1 mg/kg S(+)-ketamine epidural group (1 NKG) received 0.1 mg/kg epidural S(+)-ketamine and transdermal nitroglycerin. Pain and adverse effects were evaluated using a 10-cm visual analog scale (VAS). MEASUREMENTS AND MAIN RESULTS: The groups were demographically the same. Sensory anesthetic level and VAS score for pain at the time of first rescue medication were similar among groups. The time to first rescue analgesic (min) was less in both the CG and the NG groups compared with the other groups (p < 0.05). Epidural S(+)-ketamine resulted in analgesia to both groups (1 KG < 2 KG; p < 0.05). The 1 NKG and the 2 KG displayed similar analgesia (p > 0.05). The CG required more rescue analgesics in 24 hours compared with the patients who received epidural S(+)-ketamine (p < 0.02). CONCLUSIONS: Epidural S(+)-ketamine resulted in antinociception, which was enhanced by transdermal nitroglycerin.     

Caudal neostigmine,bupivacaine, and their combination for postoperative pain management after hypospadias surgery in children

In a randomized, double-blinded study, we examined the analgesic efficacy of caudal neostigmine, bupivacaine, or a mixture of both drugs in 60 children. After the induction of general anesthesia, children were allocated randomly into three groups (n = 20) to receive a caudal injection of either 0.25% bupivacaine 1 mL/kg, with or without neostigmine 2 micro g/kg, or neostigmine 2 micro g/kg in normal saline 1 mL/kg. Intraoperatively, children receiving caudal bupivacaine or a bupivacaine/neostigmine mixture maintained hemodynamic stability, required less inhaled anesthetics, and had a shorter recovery time compared with the caudal neostigmine alone. Postoperatively, the caudal bupivacaine/neostigmine mixture resulted in superior analgesia compared with the other two groups. Recovery to first rescue analgesic times were (mean +/- SD) 22.8 +/- 2.9 h, 8.1 +/- 5.9 h, and 5.2 +/- 2.1 h in the bupivacaine/neostigmine, bupivacaine, and neostigmine groups, respectively (P < 0.001). In addition, the bupivacaine and neostigmine groups received more doses of paracetamol than the bupivacaine/neostigmine group to maintain adequate analgesia in the first 24 postoperative h. Postoperative vomiting occurred in 25%, 10%, and 30% in the caudal bupivacaine/neostigmine, bupivacaine, and neostigmine groups, respectively (P < 0.01). We conclude that caudal neostigmine 2 micro g/kg provides postoperative analgesia comparable to caudal bupivacaine in children undergoing hypospadias repair surgery. IMPLICATIONS: Caudal neostigmine 2 micro g/kg provides postoperative analgesia comparable to caudal bupivacaine in children undergoing hypospadias repair surgery. Co-administration of the two drugs is associated with extended postoperative analgesia and reduced need for supplementary analgesics.