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 microg x kg(-1) x min(-1). The Coadministration group (n = 19) received propofol 33 +/- 13 microg x kg(-1) x min(-1) and ketamine 3.7 +/- 1.5 microg x kg(-1) x min(-1). Respiration was assessed by using end-expiratory PCO(2) 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 PCO(2) 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.

Midazolam attenuates ketamine-induced abnormal perception and thought process but not mood changes.

PURPOSE: To determine the effects of midazolam, 30 ngxmL(-1), on altered perception, mood, and cognition induced by ketamine. METHODS: After ketamine was administered to achieve target concentrations of 50, 100, or 150 ngxmL in 11 volunteers, perception, mood, and thought process were assessed by a visual analog scale. Mini-Mental State examination (MMSE) assessed cognition. Boluses of midazolam, 30, 14.5, and 12 microgxkg(-1), were injected every 30 min to maintain the plasma concentration at 30 ngxmL(-1), which was reached 30 min after each injection. RESULTS: Ketamine produced changes in perception about the body (P < 0.01, 0.001, and 0.0001 at 30, 60, and 90 min), surroundings (P < 0.01 and 0.0001 at 60 and 90 min), time (P < 0.002 and 0.0001 at 60 and 90 min), reality (P < 0.001 and 0.0001 at 60 and 90 min), sounds (P < 0.002 at 90 min), and meaning (P < 0.05 at 90 min). Subjects felt less energetic and clearheaded (P < 0.02 and 0.05) during ketamine, midazolam, and their co-administration. Ketamine impaired thought process (P < 0.003 and 0.0001 at 60 and 90 min). Ketamine and midazolam decreased mean total MMSE and recall scores (P < 0.001 for both). Co-administration reduced the number of subjects with perceptual (body, P < 0.01 and 0.001 at 30 and 60 min) and thought process abnormalities. Within the range of observation, co-administration did not affect the changes in mood or recall. CONCLUSION: Midazolam attenuates ketamine-induced changes in perception and thought process.

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.

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 microg fentanyl (n = 24), followed by the same opiate (125 microg/ml morphine or 25 microg/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.

Intra-articular morphine after arthroscopic knee operation.

Reports on pain relief with intra-articular morphine after arthroscopic knee operation are conflicting. To assess the long-term antinociceptive effect of intraarticular morphine, we studied pain at rest, pain on standing and ability to walk for 7 days after intraarticular injection of bupivacaine 100 mg (group 1, n = 11), bupivacaine 100 mg and morphine 1 mg (group 2, n = 10) and bupivacaine 100 mg and morphine 3 mg (group 3, n = 10) at the end of operation. Pain and walking were assessed by visual analogue and walking scales, respectively. Pain was treated with morphine i.v. in the recovery room and Tylenol No. 3 after discharge. Assessments were made before operation, and 1, 3, 6 and 12 h after injection and on days 1-7 after operation. There were significant differences between the groups in pain scores (pain at rest, P < 0.05; pain on standing, P < 0.01). The pain scores in group 3 were lower than those in group 1. The differences in pain scores at rest were significant at 12 h and on day 1 after operation and differences in pain scores on standing were significant at 12 h and on days 1 and 2 after operation. The scores in group 2 were intermediate between those in groups 1 and 3. The walking scores in group 3 were significantly better than those in group 1 at 12 h. The amount of analgesics received in groups 2 and 3 was significantly less than that in group 1 until day 3 after operation.(ABSTRACT TRUNCATED AT 250 WORDS)

Auditory steady-state response, upper facial EMG, EEG and heart rate as predictors of movement during isoflurane-nitrous oxide anaesthesia.

We have studied the relationship between patient movement and changes in the auditory steady-state evoked potential, upper facial muscle electromyogram (FEMG), electroencephalographic-zero crossing frequency (EEG-ZCF) and heart rate during emergence from anaesthesia. Twelve healthy patients underwent surgery during stable isoflurane-nitrous oxide-oxygen anaesthesia without neuromuscular block. After skin closure, anaesthesia was discontinued abruptly while mechanical ventilation was continued until the patient moved. The magnitude of change in each physiological signal was evaluated in decibels (dB). Both the auditory steady state evoked potential and FEMG showed significant increases in amplitude during the last 5-min period before movement (6.1 and 10.7 dB, respectively). EEG-ZCF increased rapidly after anaesthesia was discontinued (2.5 dB) but there was no further increase in activity before movement. Heart rate did not change before movement. The use of the decibel transformation offers a promising method of displaying and interpreting changes in physiological variables during anaesthesia.

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.

Side effects during continuous epidural infusion of morphine and fentanyl.

Respiratory effects, nausea, somnolence, and pruritus were compared during a 48-hr period of continuous epidural morphine (n = 34) and fentanyl (n = 32) infusion in 66 patients following elective total replacement of the hip or knee joint. Respiratory effects were assessed by PaCO2. Side effects were assessed by visual analogue scale and considered to be present when the score was above 30. Assessment was made at preoperative visits then 3, 6, 12, 24, 36, and 48 hr after the epidural injection. The bolus dose and subsequent infusion rate were 3,900 +/- 1,300 micrograms and 427 +/- 213 micrograms.hr-1 for morphine, and 85 +/- 46 micrograms and 56 +/- 27 micrograms.hr-1 for fentanyl. Pain relief was similar in both groups. In the morphine group, PaCO2 elevation and nausea occurred over a period of more than 12 hr (P less than 0.05). In the fentanyl group, there was no PaCO2 change, and nausea was confined to the first few hours. Nausea was more severe (P less than 0.01 at six hours and more frequent (24 hr cumulative incidence, 53 vs 28%, P less than 0.05) in the morphine group. Somnolence was prominent within several hours in two-thirds of patients in both groups. Somnolence continued to decline thereafter in the morphine group, but it was demonstrable in approximately half of the patients throughout the second day in the fentanyl group. The incidence was higher in the fentanyl group at the 48th hr (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac sympathetic tone in anaesthetized diabetics.

To assess cardiac sympathetic nervous function in diabetics, the heart rates attained following a pharmacological dose of intravenous atropine, 23 micrograms.kg-1, were studied under N2O, isoflurane anaesthesia in diabetics (n = 21) and nondiabetics (n = 30). Atropine-induced heart rate in diabetics was significantly lower than that in nondiabetics (95 +/- 14 (SD) bpm vs 109 +/- 12 bpm, P less than 0.001) and were closely related to preoperative orthostatic diastolic blood pressure change (r = 0.60, P less than 0.01). There was some correlation between the atropine-induced heart rate and preoperative RR-variation in diabetics (r = 0.50, P less than 0.05). The findings suggest that cardiac sympathetic function may also be impaired in diabetics with orthostatic hypotension.

Stroke volume measurements by electrical bioimpedance and echocardiography in healthy volunteers.

To evaluate the validity of three equations for estimation of thoracic electrical field size in a new bioimpedance algorithm, stroke volume (SV) as calculated by these equations was compared with that calculated by Doppler echocardiography in 48 healthy volunteers, both lean and obese. When the volume of electrically participating tissue was estimated from body height (modified Sramek) or body height corrected for body habitus (Sramek-Bernstein), there was considerable variation between bioimpedance and Doppler stroke volumes. When the volume of electrically participating tissue was estimated from the actual measurement of the height of the thorax and the circumference at the base of the thorax, the variation in SV differences decreased substantially (Sramek equation), although still considerable for clinical use, and there was no relationship between SV thus obtained and body habitus. Analysis of calculated stroke indices derived by our Doppler echocardiographic standard, as compared with values in the literature, revealed a systematic underestimation. We conclude that the original Sramek equation systematically underestimates SV by 15% to 20%, and the modified Sramek and Sramek-Bernstein equations systematically underestimates SV by 15% to 20%, and the modified Sramek and Sramek-Bernstein equations systematically overestimate SV in females by about 15%, but provide SV values in males in the predicted range. Further studies on the current assumption that the electrical field size is a truncated cone may improve precision of the bioimpedance method.

Peripheral somatic sensory neuropathy and skin galvanic response in the feet of patients with diabetes.

The relationship between abnormality in the peripheral sympathetic nervous system (skin galvanic response) and in the peripheral somatic sensory nerve fibers was studied in the lower extremities of 51 patients with diabetes. Deficits in temperature and pain sensations (the small sensory nerve fibers) were related to abnormal sympathetic nervous function (temperature sensation, p less than 0.001; pain sensation, p less than 0.05). The deficits in temperature sensation, in particular, predicted abnormal sympathetic nervous function reliably and vice versa. There was no relationship between deficits in touch and vibration sensations (the large sensory nerve fibers) and abnormal sympathetic nervous function. There was a relationship between skin galvanic response and RR-variation (p less than 0.01). However, abnormality in RR-variation was not related to the deficits in any of the four sensory modalities.

Peripheral plasma levels of prostaglandin metabolites, cortisol and prolactin in women undergoing falope ring application and tubal cautery.

The levels of 11-deoxy-13,14-dihydro-15-keto-11 beta, 16 xi-cyclo PGE2 (bicyclo PGEM), 13,14-dihydro-15-keto PGF 2 alpha (PGFM), cortisol and prolactin were measured by radioimmunoassays in five serial plasma samples collected from fourteen patients undergoing falope ring application and three patients undergoing tubal electrocautery. Bicyclo PGEM, PGFM and cortisol levels were unchanged regardless of the type of tubal occlusion procedure or the type of anesthesia administered (7 received general and 10 local anesthesia). Prolactin levels, on the other hand, markedly increased. The increase was greatest in women that received general anesthesia. The lack of change in bicyclo PGEM and PGFM in peripheral plasma would suggest a local transfer of PGs produced by injured tubal tissue to other parts of the tube and the uterus resulting in increased contractions and pelvic pain.