Kentaro Tsueda

SMALL-DOSE KETAMINE ENHANCES MORPHINE-INDUCED ANALGESIA AFTER OUTPATIENT SURGERY

UNLABELLED Small-dose ketamine may enhance the analgesic effect of opiates. We studied the effect of IV coadministration of small-dose ketamine 50-100 microg/kg with morphine 50 microg/kg on postoperative morphine requirements and pain in 140 patients undergoing outpatient surgery. Midazolam 1-2 mg was administered in the holding area. Anesthesia was induced with propofol 2-2.5 mg/kg and was maintained with desflurane in a nitrous oxide/oxygen mixture. Patients received morphine 50 microg/kg with placebo (Group 1, n = 35) or ketamine 50 microg/kg IV (Group 2, n = 35), 75 microg/kg IV (Group 3, n = 35), or 100 microg/kg IV (Group 4, n = 35) 15 min before the end of the operation. Pain and drowsiness were assessed using visual analog scales on arrival in the recovery room, then every 15 min until the time of discharge to phase 2 recovery (phase 1 recovery). Morphine consumption in Groups 3 and 4 was approximately 40% less than that in the control group (91+/-9 and 89+/-8 microg/kg vs. 145+/-9 microg/kg; P<0.05 for both). Pain scores in Groups 3 and 4 were approximately 35% less than those in the control group at all time periods (P<0.0001 for all). There was no significant group difference in drowsiness scores. Small-dose ketamine 75-100 microg/kg IV, enhanced morphine-induced analgesia after outpatient surgery. Simultaneous use of small doses of ketamine with morphine enhances the pain relief produced by morphine. IMPLICATIONS Simultaneous use of small doses of ketamine with morphine enhances the pain relief produced by morphine.

Increased sensitivity to thermal pain and reduced subcutaneous lidocaine efficacy in redheads.

Background:Anesthetic requirement in redheads is exaggerated, suggesting that redheads may be especially sensitive to pain. Therefore, the authors tested the hypotheses that women with natural red hair are more sensitive to pain and that redheads are resistant to topical and subcutaneous lidocaine. Methods:The authors evaluated pain sensitivity in red-haired (n = 30) or dark-haired (n = 30) women by determining the electrical current perception threshold, pain perception, and maximum pain tolerance with a Neurometer CPT/C (Neurotron, Inc., Baltimore, MD). They evaluated the analogous warm and cold temperature thresholds with the TSA-II Neurosensory Analyzer (Medoc Ltd., Minneapolis, MN). Volunteers were tested with both devices at baseline and with the Neurometer after 1-h exposure to 4% liposomal lidocaine and after subcutaneous injection of 1% lidocaine. Data are presented as medians (interquartile ranges). Results:Current perception, pain perception, and pain tolerance thresholds were similar in the red-haired and dark-haired women at 2,000, 250, and 5 Hz. In contrast, redheads were more sensitive to cold pain perception (22.6 [15.1–26.1] vs. 12.6 [0–20]°C; P = 0.004), cold pain tolerance (6.0 [0–9.7] vs. 0.0 [0.0–2.0]°C; P = 0.001), and heat pain (46.3 [45.7–47.5] vs. 47.7 [46.6–48.7]°C; P = 0.009). Subcutaneous lidocaine was significantly less effective in redheads (e.g., pain tolerance threshold at 2,000-Hz stimulation in redheads was 11.0 [8.5–16.5] vs. > 20.0 (14.5 to > 20) mA in others; P = 0.005). Conclusion:Red hair is the phenotype for mutations of the melanocortin-1 receptor. Results indicate that redheads are more sensitive to thermal pain and are resistant to the analgesic effects of subcutaneous lidocaine. Mutations of the melanocortin-1 receptor, or a consequence thereof, thus modulate pain sensitivity.

The Effects of Small-Dose Ketamine on Propofol Sedation: Respiration, Postoperative Mood, Perception, Cognition, and Pain

We compared the effects of coadministration of propofol and small-dose ketamine to propofol alone on respiration during monitored anesthesia care. In addition, mood, perception, and cognition in the recovery room, and pain after discharge were evaluated. In the Propofol group (n = 20), patients received propofol 38 ± 24 &mgr;g · kg−1 · min−1. The Coadministration group (n = 19) received propofol 33 ± 13 &mgr;g · kg−1 · min−1 and ketamine 3.7 ± 1.5 &mgr;g · kg−1 · min−1. Respiration was assessed by using end-expiratory Pco2 measurements at nasal prongs. After surgeries, mood, perception, and thought were assessed by using visual analog scales, and cognition was assessed by Mini-Mental State Examination (MMSE). Pain after discharge was assessed by a five-point rating scale in the evening for 5 days. End-expiratory Pco2 was lower in the Coadministration group (P < 0.0001). Mood and MMSE scores were higher in the Coadministration group (P < 0.004 and P = 0.001, respectively). Pain scores and analgesic consumption after discharge were less in the Coadministration group (P = 0.0004 and P < 0.0001, respectively). We conclude that coadministration of small-dose ketamine attenuates propofol-induced hypoventilation, produces positive mood effects without perceptual changes after surgery, and may provide earlier recovery of cognition.

Mood during Epidural Patient-controlled Analgesia with Morphine or Fentanyl

Background Mood states during epidural opioids are not known. The authors studied the change in mood during the 48‐h period of epidural morphine and epidural fentanyl in 47 patients after elective hip or knee joint arthroplasty. Methods An epidural catheter was inserted at the L2‐L3 or L3‐L4 interspace. Anesthesia was induced with thiopenthal and maintained with isoflurane and nitrous oxide. One hour before the conclusion of the operation, patients received an epidural bolus injection of 2 mg morphine (n = 23) or 100 micro gram fentanyl (n = 24), followed by the same opiate (125 micro gram/ml morphine or 25 micro gram/ml fentanyl) epidurally delivered by a patient‐controlled analgesia (PCA) pump in the postoperative period for 48 h. Mood was assessed using the bipolar form of the Profile of Mood States before operation and 24 h, 48 h, and 72 h after operation. Results There was no significant difference in pain intensity between the groups during epidural PCA. Mood states became more positive over time in the patients who received morphine (P < 0.01 at 48 h) and negative in those who were given fentanyl (P < 0.01 at 24 and 48 h, respectively) compared with those before the operation, and they were more positive in the morphine than in the fentanyl group at 24 h, 48 h (P < 0.05), and 72 h (P < 0.01). Patients in the morphine group were more composed, agreeable, elated, confident, energetic, and clearheaded than were those in the fentanyl group (P < 0.05). There was no correlation between mood scores and pain scores in either group. There was an inverse correlation at 48 h between mood scores and plasma fentanyl concentrations (r = ‐0.58, P < 0.05). Conclusion Mood states are significantly more positive during epidural morphine PCA than they are during epidural fentanyl PCA.

The Effect of Intravenous Ranitidine and Metoclopramide on Behavior, Cognitive Function, and Affect

Both ranitidine and metoclopramide produce neuropsychiatric side effects. Concomitant use of these drugs preoperatively may produce adverse behavioral and emotional changes. Therefore, in 123 unpremedicated patients undergoing tubal occlusion, behavior, cognitive function, and affect were studied before and after a 2‐min intravenous injection of placebo (n = 30), ranitidine 50 mg (n = 32), metoclopramide 10 mg (n = 30), or both ranitidine 50 mg and metoclopramide 10 mg (n = 31). Cognitive function was evaluated by the responses to 11 statements devised to assess attitude toward anesthesia and surgery. Affect was assessed by the word chosen out of 11 word‐pairs as best describing the feelings at the time. After ranitidine injection, one patient seemed restless and five seemed drowsy. The changes were associated with subjective feelings of agitation (P < 0.05) and restlessness (P < 0.05). After metoclopramide injection, 6 (20%) developed akathisia, 13 (43.3%) seemed restless, and 8 (26.7%) seemed drowsy. The changes were associated with subjective sensation of jumpiness (P < 0.01) and discomfort (P < 0.05). When both ranitidine and metoclopramide were injected, 10 (32.3%) developed akathisia, 4 (12.4%) seemed restless, and 11 (35.5%) seemed drowsy. The changes were associated with subjective feelings of agitation (P < 0.05), jumpiness (P < 0.05), restlessness (P < 0.01), and upset (P < 0.05). Akathisia, a side effect of metoclopramide, seemed to be more prominent when ranitidine was added.

Effects of meclofenamate and acetaminophen on abdominal pain following tubal occlusion.

To test the hypothesis that the postoperative abdominal pain of tubal occlusion is mediated by prostaglandins, the effects of meclofenamate, a potent inhibitor of cyclooxygenase, on postoperative analgesia and incidence of abdominal pain were compared with those of acetaminophen, a weak inhibitor of prostaglandin activity. One hundred patients undergoing tubal occlusion under local anesthesia were studied. The patients were randomly divided into four equal groups: control; acetaminophen, 1300 mg; meclofenamate, 100 mg; meclofenamate, 200 mg. The fallopian tubes were occluded by electrocautery in 47 patients and by application of Falope rings in 53 patients. Both acetaminophen and meclofenamate provided substantial analgesia for 4 hours after the operation (p less than 0.05). Meclofenamate reduced the incidence of abdominal pain by one half (p less than 0.02), but acetaminophen did not. These results suggest that a portion of pain relief achieved by meclofenamate may be due to suppression of myosalpingian and/or myometrial contractions, a process mediated by prostaglandins.

Severe laryngospasm at tracheal extubation in a patient with superior laryngeal nerve injury.

E pisodic laryngospasm is often associated with occult gastroesophageal reflux disease (1,2). A recent report described six cases of hypersensitive laryngeal reflex developing a few weeks to 12 months after laryngeal nerve injury. Symptoms were paroxysms of coughing and stridor that progressed in some to brief episodes of complete airway obstruction (3), suggesting that laryngeal nerve injury may be an etiology in the syndrome of episodic laryngospasm. We report a severe laryngospasm at tracheal extubation in a patient with evidence of superior laryngeal nerve injury, presumably from thyroid lobectomy performed 5 yr earlier. The laryngospasm may have represented laryngeal hypersensitivity.