The effects of epidural insertion site and surgical procedure on plasma lidocaine concentration

We compared the plasma lidocaine concentrations associated with continuous epidural infusion at different insertion sites in patients during surgery using epidural plus general anesthesia. In Study 1, there were 12 patients in each of four surgical groups in whom blood loss was expected to be <400 mL. The four groups were as follows: the lower extremity, the lower abdomen, the upper abdomen, and the lung. Liver surgery was excluded from Study 1. Study 2 comprised patients undergoing radical hysterectomy or radical prostatectomy (a radical operation group, n = 12) and hepatectomy (a hepatectomy group, n = 12) in whom the expected surgical blood loss was more than 1500 mL. All patients initially received 0.1 mL/kg followed by a continuous infusion of 0.1 mL. kg(-1). h(-1) of 1.5% lidocaine, and plasma concentrations of lidocaine were measured at 15, 30, 60, 90, and 120 min and every 60 min thereafter to 300 min. The plasma lidocaine concentration during surgery did not change regardless of the infusion site or the surgical site, other than the liver. The plasma concentrations of lidocaine in the hepatectomy group increased significantly at 180 min (2.9 +/- 0.6 microg/mL, P < 0.01), 240 min (3.5 +/- 0.7 microg/mL, P < 0.01), and 300 min (3.6 +/- 0.74 microg/mL, P < 0.01) compared with that at 15 min (2.0 +/- 0.3 microg/mL), and these values were significantly larger than those in all other groups.     

Perioperative intravenous lidocaine has preventive effects on postoperative pain and morphine consumption after major abdominal surgery

Sodium channel blockers are approved for IV administration in the treatment of neuropathic pain states. Preclinical studies have suggested antihyperalgesic effects on the peripheral and central nervous system. Our objective in this study was to determine the time course of the analgesic and antihyperalgesic mechanisms of perioperative lidocaine administration. Forty patients undergoing major abdominal surgery participated in this randomized and double-blinded study. Twenty patients received lidocaine 2% (bolus injection of 1.5 mg/kg in 10 min followed by an IV infusion of 1.5 mg. kg(-1). h(-1)), and 20 patients received saline placebo. The infusion started 30 min before skin incision and was stopped 1 h after the end of surgery. Lidocaine blood concentrations were measured. Postoperative pain ratings (numeric rating scale of 0-10) and morphine consumption (patient-controlled analgesia) were assessed up to 72 h after surgery. Mean lidocaine levels during surgery were 1.9 +/- 0.7 microg/mL. Patient-controlled analgesia with morphine produced good postoperative analgesia (numeric rating scale at rest, 相似文献   

Plasma lidocaine concentrations during epidural blockade with isoflurane or halothane anesthesia.

Because isoflurane maintains hepatic blood flow at higher flows than halothane, we proposed that the elimination of lidocaine would be different between these two volatile anesthetics. The plasma lidocaine concentrations were determined in 14 female patients undergoing epidural blockade plus isoflurane anesthesia and compared with those obtained during halothane anesthesia for lower abdominal surgery. General anesthesia was maintained with isoflurane (0.46% +/- 0.04% [mean +/- SE] inspired, n = 7) or halothane (0.48% +/- 0.05% inspired, n = 7) and 67% nitrous oxide in oxygen. All patients received 2% lidocaine solution, 10 mL as a bolus dose and continuous administration at a rate of 10 mL/h, through the epidural catheter. The plasma lidocaine concentrations over 180 min after the epidural injection in patients receiving isoflurane were similar to those in patients receiving halothane. The results suggest that low inspired concentrations of isoflurane do not reduce plasma lidocaine concentrations in patients during epidural blockade, compared with halothane.     

Propofol does not inhibit lidocaine metabolism during epidural anesthesia

Propofol is sometimes used in combination with epidural anesthesia with lidocaine. In this study, we investigated the effect of propofol on the plasma concentration of lidocaine and its principal metabolites during epidural anesthesia with lidocaine. Thirty-two patients were randomly allocated to receive either propofol or sevoflurane anesthesia (n = 16 each). In the propofol group, anesthesia was maintained with a target concentration of propofol of 4 microg/mL. In the sevoflurane group, anesthesia was maintained with 1.5% sevoflurane. Lidocaine was administered epidurally in an initial dose of 5 mg/kg, followed by a continuous infusion at 2.5 mg x kg(-1) x h(-1). Free components of plasma lidocaine and its metabolites-monoethylglycinexylidide (MEGX) and glycinexylidide (GX)-were measured 30, 60, 120, and 180 min after the initiation of continuous epidural injection by using high-performance liquid chromatography. Free lidocaine, MEGX, and GX were separated from 2 mL of plasma by ultrafiltration filter units. Hemodynamic data were similar between groups. The plasma concentrations of free lidocaine were not significantly different between groups. The ratios of free MEGX to free lidocaine and free GX to free MEGX were not different between groups. In conclusion, propofol does not alter the metabolism of epidural lidocaine compared with sevoflurane.     

A dopamine infusion decreases propofol concentration during epidural blockade under general anesthesia

PURPOSE: It is common clinical practice to use dopamine to manage the reduction in blood pressure accompanying epidural blockade. As propofol is a high-clearance drug, propofol concentrations can be influenced by cardiac output (CO). The purpose of the present study was to investigate the effects of dopamine infusions on propofol concentrations administered by a target-controlled infusion system during epidural block under general anesthesia. METHODS: 12 patients undergoing abdominal surgery were enrolled in this study. Anesthesia was induced with propofol and vecuronium 0.1 mg.kg(-1), and maintained using 67% nitrous oxide, sevoflurane in oxygen and constant infusion of propofol. Propofol was administered to all subjects via target-controlled infusion to achieve a propofol concentration at 6.0 microg.mL(-1) at intubation and 2.0 microg.mL(-1) after intubation. Before and after the administration of 10 mL of 1.5% mepivacaine from the epidural catheter and dopamine infusion at 5 microg.kg(-1).min(-1), CO and effective liver blood flow (LBF) were measured using indocyanine green. Blood propofol concentration was also determined using high-performance liquid chromatography. RESULTS: At one hour after epidural block and dopamine infusion, CO was significantly increased from 4.30 +/- 1.07 L.min(-1) to 5.82 +/- 0.98 L.min(-1) (P < 0.0001), and effective LBF was increased 0.75 +/- 0.17 L.min(-1) to 0.96 +/- 0.18 L.min(-1) (P < 0.0001). Propofol concentration was significantly decreased from 2.13 +/- 0.24 microg.mL(-1) to 1.59 +/- 0.29 microg.mL(-1) (P < 0.0001). CONCLUSIONS: Propofol concentrations decrease with an increase in CO, suggesting the possibility of inadequate anesthetic depth following catecholamine infusion during propofol anesthesia.     

Does epidural anesthesia have general anesthetic effects? A prospective, randomized, double-blind, placebo-controlled trial

BACKGROUND: Clinically, patients require surprisingly low end-tidal concentrations of volatile agents during combined epidural-general anesthesia. Neuraxial anesthesia exhibits sedative properties that may reduce requirements for general anesthesia. The authors tested whether epidural lidocaine reduces volatile anesthetic requirements as measured by the minimum alveolar concentration (MAC) of sevoflurane for noxious testing cephalad to the sensory block. METHODS: In a prospective, randomized, double-blind, placebo-controlled trial, 44 patients received 300 mg epidural lidocaine (group E), epidural saline control (group C), or epidural saline-intravenous lidocaine infusion (group I) after premedication with 0.02 mg/kg midazolam and 1 microg/kg fentanyl. Tracheal intubation followed standard induction with 4 mg/kg thiopental and succinylcholine 1 mg/kg. After 10 min or more of stable end-tidal sevoflurane, 10 s of 50 Hz, 60 mA tetanic electrical stimulation were applied to the fifth cervical dermatome. Predetermined end-tidal sevoflurane concentrations and the MAC for each group were determined by the up-and-down method and probit analysis based on patient movement. RESULTS: MAC of sevoflurane for group E, 0.52+/-0.18% (+/- 95% confidence interval [CI]), differed significantly from group C, 1.18+/-0.18% (P < 0.0005), and from group I, 1.04+/-0.18% (P < 0.001). The plasma lidocaine levels in groups E and I were comparable (2.3+/-1.0 vs. 3.0+/-1.2 microg/ml +/- SD). CONCLUSIONS: Lidocaine epidural anesthesia reduced the MAC of sevoflurane by approximately 50%. This MAC sparing is most likely caused by indirect central effects of spinal deafferentation and not to systemic effects of lidocaine or direct neural blockade. Thus, lower concentrations of volatile agents than those based on standard MAC values may be adequate during combined epidural-general anesthesia.     

Plasma lidocaine concentrations during continuous thoracic epidural anesthesia after clonidine premedication in children.

There is no report concerning oral clonidine's effects on epidural lidocaine in children. Therefore, we performed a study to assess the concentrations of plasma lidocaine and its major metabolite (monoethylglycinexylidide [MEGX]) in children receiving continuous thoracic epidural anesthesia after oral clonidine premedication. Ten pediatric patients, aged 1-9 yr, were randomly allocated to the Control or Clonidine 4 microg/kg group (n = 5 each). Anesthesia was induced and maintained with sevoflurane in oxygen and air (FIO2 40%). Epidural puncture and tubing were carefully performed at the Th11-12 intervertebral space. An initial dose of 1% lidocaine (5 mg/kg) was injected through a catheter into the epidural space, followed by 2.5 mg x kg(-1) x h(-1). Plasma concentrations of lidocaine and MEGX were measured at 15 min, 30 min, and every 60 min for 4 h after the initiation of continuous epidural injection. The concentrations of lidocaine and MEGX were measured using high-pressure liquid chromatography with ultraviolet detection. Hemodynamic variables were similar between members of the Control and Clonidine groups during anesthesia. The Clonidine group showed significantly smaller lidocaine concentrations (p < 0.05) and the concentration of MEGX tended to be smaller in the plasma of the Clonidine group for the initial 4 h after the initiation of epidural infusion. In conclusion, oral clonidine preanesthetic medication at a dose of 4 microg/kg decreases plasma lidocaine concentration in children. IMPLICATIONS: Oral clonidine decreases the plasma lidocaine concentration in children. Our finding may have clinical implications in patients receiving continuous epidural anesthesia. Additionally, perhaps an additional margin of safety regarding lidocaine toxicity is gained through the use of oral clonidine in children who will receive epidural lidocaine.     

Disappearance of wheezing during epidural lidocaine anesthesia in a patient with bronchial asthma.

BACKGROUND AND OBJECTIVES: Local anesthetics in blood absorbed from the epidural space attenuate bronchial hyperreactivity to chemical stimuli. However, it is not documented whether local anesthetics at clinically relevant concentrations improve active wheezing in patients with bronchial asthma. CASE REPORT: We managed a 60-year-old man with bronchial asthma and active wheezing under continuous epidural anesthesia using plain lidocaine. The wheezing gradually diminished 20 minutes after the epidural injection of 13 mL 2% lidocaine and completely disappeared over 155 minutes during continuous epidural injection of 2% lidocaine (6 mL/h). The plasma concentrations of lidocaine in arterial blood during the epidural anesthesia ranged from 2.5 to 3.9 microg/mL. Wheezing reappeared 55 minutes after termination of the continuous epidural injection of lidocaine. The plasma concentration of lidocaine at this time was 1.9 microg/mL. CONCLUSIONS: At clinically relevant concentrations, lidocaine in the blood absorbed from the epidural space may improve bronchospasm in patients with bronchial asthma.     

Continuous intra- and postoperative thoracic epidural analgesia attenuates brain natriuretic peptide release after major abdominal surgery

We investigated whether blocking afferent nociceptive inputs by continuous intra- and postoperative thoracic epidural analgesia (TEA) would decrease plasma concentrations of brain natriuretic peptide (BNP) in patients who were at risk for, or had, coronary artery disease. Twenty-eight patients undergoing major abdominal surgery received either general anesthesia supplemented with a continuous thoracic epidural infusion of 1.25 mg/mL bupivacaine and 1 microg/mL sufentanil (n = 14; TEA) or general anesthesia followed by IV patient-controlled analgesia (n = 14; IV PCA). Visual analog scale pain scores, hemodynamics, plasma catecholamines, cardiac troponin T, atrial natriuretic peptide (ANP), and BNP were serially measured preoperatively, 90 min after skin incision, at arrival in the intensive care unit, and in the morning of the first, second, and third postoperative day. Dynamic visual analog scale scores were significantly less in the TEA group. TEA reduced the postoperative heart rate without affecting other hemodynamic variables. Plasma epinephrine increased perioperatively in both groups but was significantly lower in the TEA group. Baseline ANP and BNP concentrations were similar between groups (TEA 3.4 +/- 1.8 and 27.0 +/- 12.3 pg/mL; IV PCA 3.1 +/- 2.0 and 25.9 +/- 13.0 pg/mL, respectively). ANP and BNP increased perioperatively in both groups, with significantly lower postoperative BNP levels in TEA patients (TEA 92.1 +/- 31.9 pg/mL; IV PCA 161.2 +/- 44.7 pg/mL). No such difference was observed in plasma ANP concentrations. Plasma cardiac troponin T concentrations were within normal limits in both groups at all times. We conclude that continuous perioperative TEA using local anesthetics and opioids attenuated the release of BNP in patients undergoing major abdominal surgery who were at risk for, or had, coronary artery disease.     

Epidural morphine delays the onset of tourniquet pain during epidural lidocaine anesthesia

We conducted a randomized, double-blinded study to examine the onset time of tourniquet pain during epidural lidocaine anesthesia either with or without morphine in the epidural solution. Forty-five patients undergoing knee surgery with a thigh tourniquet were randomly allocated into 3 groups of 15 patients each: epidural morphine (EM; epidural administration of 17 mL of 2% lidocaine plus 2 mg of morphine, followed by IV injection of 0.2 mL of normal saline), IV morphine (IVM; 17 mL of 2% lidocaine plus 0.2 mL of normal saline, followed by IVM 2 mg IV), and control (17 mL of 2% lidocaine plus 0.2 mL of normal saline, followed by 0.2 mL of normal saline IV). The onset time of tourniquet pain was recorded. The level of sensory block was determined by the pinprick method at the occurrence of tourniquet pain. Hemodynamic changes and side effects of EM were also recorded. The onset time of tourniquet pain from both the epidural injection and the tourniquet inflation were significantly longer in the EM group (103 +/- 15 min and 80 +/- 15 min, respectively) compared with the IVM group (74 +/- 12 min and 50 +/- 12 min, respectively; P < 0.05) and the Control group (67 +/- 9 min and 45 +/- 9 min, respectively; P < 0.05). The level of sensory block at the onset of tourniquet pain and hemodynamic changes were not different among the three groups. Only two and three patients in the EM group complained of nausea/vomiting and pruritus, respectively. Respiratory depression was not observed in any patient. We conclude that epidural injection of the mixture of 2 mg of morphine and 2% lidocaine solution delayed the onset of tourniquet pain during epidural lidocaine anesthesia without significant morphine-related side effects. IMPLICATIONS: We examined the effect of epidural morphine on the onset of tourniquet pain during epidural lidocaine anesthesia. We found that the addition of 2 mg of morphine to epidural 2% lidocaine significantly delayed the onset of tourniquet pain without increasing morphine-related side effects.     

Ornipressin (Por 8): An efficient alternative to counteract hypotension during combined general/epidural anesthesia

We sought to evaluate the efficacy and side effect profile of a small dose of ornipressin, a vasopressin agonist specific for the V1 receptor, administered to reverse the hypotension associated with combined general/epidural anesthesia. A total of 60 patients undergoing intestinal surgery were studied. After the induction of anesthesia, 7-8 mL of bupivacaine 0.5% with 2 microg/kg clonidine and 0.05 microg/kg sufentanil after an infusion of 5 mL of bupivacaine 0.06% with 0.5 microg x kg(-1) x h(-1) clonidine and 0.1 microg/h of sufentanil were administered by an epidural catheter placed at T7-8 vertebral interspace. When 20% reduction of baseline arterial blood pressure developed, patients were randomly assigned to receive, in a double-blinded design, dopamine started at 2 microg x kg(-1) x min(-1), norepinephrine started at 0.04 microg x kg(-1) x min(-1), or ornipressin started at 1 IU/h. Fifteen patients presenting without hypotension were used as control subjects. Beside routine monitoring, S-T segment analysis, arterial lactacidemia, and gastric tonometry were performed. Ornipressin restored arterial blood pressure after 8 +/- 2 vs 7 +/- 3 min in the norepinephrine group and 11 +/- 3 min in the dopamine group (P < 0.05). This effect was achieved with 2 IU/h of ornipressin in most of the patients (11 of 15). Ornipressin did not induce any modification of the S-T segment; however, it significantly increased intracellular gastric PCO(2) (P < 0.05), indicating splanchnic vasoconstriction. Implications: In the population studied, small-dose ornipressin was effective to restore arterial blood pressure without causing major ischemic side effects.     

Epidural fentanyl speeds the onset of sensory block during epidural lidocaine anesthesia

BACKGROUND AND OBJECTIVES: Shortening the onset time of sensory block is a practical goal to improve the quality of epidural anesthesia. The addition of fentanyl to a local anesthetic solution is widely used during epidural anesthesia. This randomized double-blind study examined the onset time of sensory block during epidural lidocaine anesthesia with and without added fentanyl to the epidural solution. METHODS: Thirty-six young male patients undergoing knee arthroscopy were randomly allocated into 3 groups of 12 patients each: epidural fentanyl (EF, epidural administration of 17 mL of 2% lidocaine plus 100 microg fentanyl and followed by intravenous (IV) injection of 2 mL of normal saline); IV fentanyl (IF, epidural administration of 17 mL of 2% lidocaine plus 2 mL of normal saline and followed by IV injection of 100 microg of fentanyl); and control (C, epidural administration of 17 mL of 2% lidocaine plus 2 mL of normal saline and followed by IV injection of 2 mL of normal saline). The sensory block was assessed by pinprick method. The hemodynamic changes, postepidural shivering, and side effects of epidural fentanyl were also recorded. RESULTS: There was no difference in the distribution of age, weight, and height among the 3 groups. The onset time of sensory block up to T(10) dermatome was significantly more rapid in the EF group (8.3 +/- 3.7 minutes) than that of the IF group (13.1 +/- 4.2 minutes, P <.05) or C group (14.2 +/- 5.4 minutes, P <.05). The upper level of sensory block was also significantly higher in the EF group. Although the incidence of shivering was lower in the EF group, this did not reach statistical significance. Postepidural arterial blood pressures and heart rates were no different among the 3 groups. No nausea, vomiting, pruritus, respiratory depression, urinary retention, or hypotension were observed in any patients. CONCLUSION: Epidural injection of the mixture of 100 microg fentanyl and 2% lidocaine solution accelerated the onset of sensory block during epidural lidocaine anesthesia without increased side effects.     

Lidocaine with fentanyl, compared to morphine, marginally improves postoperative epidural analgesia in children

PURPOSE: To compare the epidural administration of fentanyl (1 microg/mL) combined with lidocaine 0.4% to preservative-free morphine for postoperative analgesia and side effects in children undergoing major orthopedic surgery. METHODS: In a prospective, double-blind study, 30 children, ASA I-II, 2-16-yr-old, were randomly allocated to receive immediately after surgery either epidural F-L (epidural infusion at a rate of 0.1-0.35 mL/kg/hr of 1 microg/mL of fentanyl and lidocaine 0.4%) or epidural M (bolus of 20 microg/kg of morphine in 0.5 mL/kg saline every eight hours). Both groups received 40 mg/kg of iv metamizol (dipyrone) every six hours. In the F-L Group, blood samples were taken on the second and third postoperative day to determine total lidocaine concentrations. Adequacy of analgesia using adapted pediatric pain scales (0-10 score) and side-effects were assessed every eight hours postoperatively. RESULTS: Resting pain scores were under 4, 95% of the time in the F-L Group and 87% of the time in the M Group (Chi square=4.674, P <0.05). The frequency of complications was very similar in both groups. The F-L Group total plasma lidocaine concentrations were directly related to the dose received, and below the toxic range in all patients. CONCLUSIONS: Postoperative epidural fentanyl with lidocaine infusion provides slightly better analgesia than conventional bolus administration of epidural morphine. Side-effects or risk of systemic toxicity were not augmented by the addition of lidocaine to epidural opioids.     

Free lidocaine concentrations during continuous epidural anesthesia in geriatric patients

BACKGROUND AND OBJECTIVES: To evaluate the effects of aging on lidocaine pharmacokinetics, the plasma concentrations of total and free lidocaine and its metabolites were measured during continuous thoracic epidural anesthesia in middle-aged (age 41 +/- 9 years, n = 7) and elderly (age 72 +/- 2 years, n = 7) male patients. METHODS: After establishment of general anesthesia, 7 mL 1.5% lidocaine with epinephrine 1:200,000 was injected into the epidural space and subsequently infused at a rate of 5 mL/h for 5 hours. Plasma concentrations of total and free lidocaine, monoethylglycinexylidide (MEGX), and glycinexylidide (GX) were measured at 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, and 300 minutes after initial lidocaine injection using high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. RESULTS: The elderly group showed a stronger upward trend in the corrected free lidocaine concentrations and lower corrected total MEGX concentrations than the middle-aged group. CONCLUSIONS: Lidocaine metabolite activity in the elderly male patients was lower than that in the middle-aged male patients. Free lidocaine concentration is prone to increase in elderly patients. Caution must be exercised during continuous thoracic epidural anesthesia combined with general anesthesia in geriatric patients.     

The efficacy of thoracic epidural neostigmine infusion after thoracotomy

Few anesthesia studies have explored perioperative continuous epidural infusion of neostigmine. We examined such a regimen in thoracotomy patients. Ninety patients were randomized to one of three groups in this double-blind trial. Before anesthesia induction, an epidural catheter was inserted in all patients at T5-8 levels under local anesthesia. Pre-neo patients received bolus 500-microg epidural neostigmine before anesthesia induction followed by infusion of 125 microg/h until the end of surgery. Post-neo patients received epidural saline during the same time periods plus bolus 500-microg epidural neostigmine at end of surgery. Patients in the control group received saline placebo during all three periods. Patients in the neostigmine groups postoperatively received patient-controlled epidural analgesia with morphine 0.02 mg/mL, bupivacaine 0.08 mg/mL, and neostigmine 7 microg/mL. Control patient-controlled epidural analgesia excluded neostigmine. Data were recorded for 6 postoperative days. Daily patient-controlled epidural analgesia consumption (mL) for Pre-neo patients was significantly less than that of post-neo and control group patients for postoperative days 1-6 (at least 10% and 16% less, respectively; P < 0.05). There was a modest decrease in pain intensity on postoperative days 3-6 for pre-neo patients versus other groups (P < 0.05). These results suggest that continuous thoracic epidural neostigmine started before anesthesia provided preemptive, preventive analgesia and an analgesic-sparing effect that improved postoperative analgesia for these patients without increasing the incidence of adverse effects.     

Epidural infusion of ropivacaine for postoperative analgesia after major orthopedic surgery: pharmacokinetic evaluation

BACKGROUND: Changing plasma protein concentrations may affect the protein binding and pharmacokinetics of drugs in the postoperative phase. Therefore, the authors evaluated the pharmacokinetics of ropivacaine, administered by 72-h epidural infusion to provide postoperative analgesia. METHODS: Twenty-eight patients, scheduled for major orthopedic surgery during combined epidural and general anesthesia received a bolus dose of ropivacaine (50 or 75 mg), followed by constant-rate (10 ml/h) epidural infusion of ropivacaine 2 mg/ml (group 1) or 3 mg/ml (group 2). Total and unbound plasma concentrations of ropivacaine and pipecoloxylidide and plasma concentrations of alpha1-acid glycoprotein were determined. In addition, the urinary excretion of ropivacaine and major metabolites was measured. RESULTS: Total plasma concentrations of ropivacaine increased steadily during the infusion, reaching 2.7 +/- 0.7 and 2.9 +/- 0.5 mg/l in groups 1 and 2 after 72 h constant-rate infusion. Unbound ropivacaine concentrations reached average steady state levels of approximately 0.06 and 0.07 mg/l. Total and unbound concentrations of pipecoloxylidide increased to 1.0 +/- 0.4 and 0.4 +/- 0.2 mg/l (group 1) and 1.2 +/- 0.4 and 0.5 +/- 0.1 mg/l (group 2) after 72 h infusion. alpha1-Acid glycoprotein concentrations initially decreased, but thereafter increased steadily to approximately twice the baseline values. CONCLUSIONS: Postoperative increases in plasma alpha1-acid glycoprotein concentrations enhance the protein binding of ropivacaine and pipecoloxylidide, causing divergence of total and unbound plasma concentrations.     

The benefits of intraoperative small-dose ketamine on postoperative pain after anterior cruciate ligament repair

In a randomized, double-blinded study with three parallel groups, we assessed the analgesic effect of intraoperative ketamine administration in 45 ASA physical status I or II patients undergoing elective arthroscopic anterior ligament repair under general anesthesia. The patients received either IV ketamine 0.15 mg/kg after the induction of anesthesia and before surgical incision and normal saline at the end of surgery (PRE group); normal saline after the induction of anesthesia and before surgical incision and IV ketamine at the end of surgery (POST group); or normal saline at the beginning and the end of surgery (CONT group). Anesthesia was performed with propofol (2 mg/kg for induction, 60-200 microg x kg(-1) x min(-1) for maintenance), sufentanil (0.2 microg/kg 10 min after surgical incision, followed by an infusion of 0.25 microg x kg(-1) x h(-1) stopped 30 min before skinclosure), vecuronium (0.1 mg/kg), and 60% N2O in O2 via a laryngeal mask airway. Postoperative analgesia was initially provided with IV morphine in the postanesthesia care unit, then with IV patient-controlled analgesia started before discharge from the postanesthesia care unit. Pain scores, morphine consumption, side effects, and degree of knee flexion were recorded over 48 h and during the first and second physiotherapy periods, performed on Days 1 and 2. Patients in the ketamine groups required significantly less morphine than those in the CONT group over 48 h postoperatively (CONT group 67.7+/-38.3 mg versus PRE group 34.3+/-23.2 mg and POST group 29.5+/-21.5 mg; P < 0.01). Better first knee flexion (CONT group 35+/-10 degrees versus PRE group 46+/-12 degrees and POST group 47+/-13 degrees; P < 0.05) and lower morphine consumption (CONT group 3.8+/-1.7 mg versus PRE group 1.2+/-0.4 mg and POST group 1.4+/-0.4 mg; P < 0.05) were noted at first knee mobilization. No differences were seen between the PRE and POST groups, except for an increase in morphine demand in the PRE versus the POST group (P < 0.05) in the second hour postoperatively. IMPLICATIONS: We found that intraoperative small-dose ketamine reduced postoperative morphine requirements and improved mobilization 24 h after arthroscopic anterior ligament repair. No differences were observed in the timing of administration. Intraoperative small-dose ketamine may therefore be a useful adjuvant to perioperative analgesic management.     

Epidural Infusion of Ropivacaine for Postoperative Analgesia after Major Orthopedic Surgery: Pharmacokinetic Evaluation

Background: Changing plasma protein concentrations may affect the protein binding and pharmacokinetics of drugs in the postoperative phase. Therefore, the authors evaluated the pharmacokinetics of ropivacaine, administered by 72-h epidural infusion to provide postoperative analgesia.

Methods: Twenty-eight patients, scheduled for major orthopedic surgery during combined epidural and general anesthesia received a bolus dose of ropivacaine (50 or 75 mg), followed by constant-rate (10 ml/h) epidural infusion of ropivacaine 2 mg/ml (group 1) or 3 mg/ml (group 2). Total and unbound plasma concentrations of ropivacaine and pipecoloxylidide and plasma concentrations of [alpha]1-acid glycoprotein were determined. In addition, the urinary excretion of ropivacaine and major metabolites was measured.

Results: Total plasma concentrations of ropivacaine increased steadily during the infusion, reaching 2.7 +/- 0.7 and 2.9 +/- 0.5 mg/l in groups 1 and 2 after 72 h constant-rate infusion. Unbound ropivacaine concentrations reached average steady state levels of approximately 0.06 and 0.07 mg/l. Total and unbound concentrations of pipecoloxylidide increased to 1.0 +/- 0.4 and 0.4 +/- 0.2 mg/l (group 1) and 1.2 +/- 0.4 and 0.5 +/- 0.1 mg/l (group 2) after 72 h infusion. [alpha]1-Acid glycoprotein concentrations initially decreased, but thereafter increased steadily to approximately twice the baseline values.     

Epidural infusion of clonidine or clonidine plus ropivacaine for postoperative analgesia in children undergoing major abdominal surgery

STUDY OBJECTIVE: To investigate the analgesic efficacy and safety of epidural infusion of clonidine in children undergoing major abdominal surgery. DESIGN: Randomized open-label study. SETTING: Postoperative anesthetic unit and pediatric ward of a metropolitan hospital. PATIENTS: Forty children aged 0 to 3 years undergoing major abdominal surgery. INTERVENTIONS: Children were randomly allocated to receive a 24-hour epidural infusion of clonidine 1 microg.mL(-1) at rate of 0.2 mL.kg -1.h -1 preceded by a bolus of 2 microg.kg -1 (CLON group) or a mixture of clonidine 1 microg.mL -1 and ropivacaine 0.1% at rate of 0.2 mL.kg -1.h -1. Both groups received intravenous (IV) ketoprofen 2 mg.kg -1 every 8 hours. Breakthrough pain was treated with IV tramadol 1 mg.kg(-1). MEASUREMENTS: Tramadol requirement, sedation and respiratory and hemodynamic changes were measured. MAIN RESULTS: Approximately 77% and 59.3% of the CLON and CLON+ROPIV groups, respectively, required no tramadol or only one dose over a 24-hour period. Except for those patients who exhibited frequent coughing during the night (4 and 5 patients in the CLON and CLON+ROPIV groups, respectively), no study patients required an analgesic and all had good sleep quality during the first night. Sedation and decreased systolic blood pressure were observed after the clonidine bolus was given. CONCLUSION: For children undergoing major abdominal surgery, the addition of epidural infusion of clonidine or clonidine plus ropivacaine to IV ketoprofen provided good analgesia quality for postoperative rest pain.     

Wound infiltration and drain lavage with ropivacaine after major shoulder surgery

Subcutaneous infiltration and wound lavage with ropivacaine is an alternative to opioids after major shoulder surgery. However, the efficacy and potential toxicity of this method remain unclear. We therefore evaluated plasma ropivacaine concentrations after shoulder infiltration and wound lavage. We subsequently quantified the efficacy of two ropivacaine concentrations. Patients undergoing major shoulder surgery were anesthetized with alfentanil and propofol. The initial patients (n = 18) received ropivacaine 7.5 mg/mL and ropivacaine plasma concentrations were measured in 15-min intervals. The subsequent 45 patients were randomly assigned to: 1) isotonic saline, 2) 3.75 mg/mL ropivacaine, or 3) 7.5 mg/mL ropivacaine. Ten milliliters of each solution was administered subcutaneously and 20 mL was injected into the wound drain which was clamped for 10 min. Supplemental postoperative pain relief was provided by patient-controlled anesthesia using the opioid piritramid (3.5-mg boluses, 6-min lock-out). Postoperative pain scores were recorded on a 100-mm visual analog scale for 4 h in the initial patients and for 10 h in the second part of the study. Unbound ropivacaine plasma concentrations peaked after 15 min at 0.08+/-0.09 microg/mL; the maximum was 0.30 microg/mL, compared with a toxic threshold of 0.6 microg/mL. In the second part of the study, pain scores were significantly lower after 3.75 mg/mL (20+/-15 mm) or 7.5 mg/mL (10+/-9 mm) ropivacaine than saline (35+/-10 mm). Piritramid requirements differed significantly in the three groups, being highest with saline and lowest with ropivacaine 7.5 mg/mL. We conclude that wound infiltration and lavage with 30 mL ropivacaine 7.5 mg/mL after major shoulder surgery resulted in very low pain scores and opioid requirement. IMPLICATIONS: Wound infiltration and lavage with 30 mL ropivacaine 7.5 mg/mL after major shoulder surgery resulted in very low pain scores and opioid requirement.