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Biomedical subjects

A N Sandler

Publications and source records attributed to A N Sandler.

At least 37 records · Page 2Linked to original sources

Multimodal analgesia before thoracic surgery does not reduce postoperative pain.

Several reports have suggested that preoperative nociceptive block may reduce postoperative pain, analgesic requirements, or both, beyond the anticipated duration of action of the analgesic agents. We have investigated, in a double-blind, placebo-controlled study, pre-emptive analgesia and the respiratory effects of preoperative administration of a multimodal antinociceptive regimen. Thirty patients undergoing thoracotomy were allocated randomly to two groups. Before surgery, the treatment group (n = 15) received morphine 0.15 mg kg-1 i.m. with perphenazine 0.03 mg kg-1 i.m. and a rectal suppository of indomethacin 100 mg, while the placebo group (n = 15) received midazolam 0.05 mg kg-1 i.m. and a placebo rectal suppository. After induction of anaesthesia, the treatment group received intercostal nerve block with 0.5% bupivacaine and adrenaline 1:200,000 (3 ml) in the interspace of the incision and in the two spaces above and two spaces below. The placebo group received identical injections but with normal saline only. The treatment group consumed significantly less morphine by patient-controlled analgesia in the first 6 h after operation, but the total dose of morphine consumed on days 2 and 3 after surgery was significantly greater in the treatment group. There were no differences between the groups in postoperative VAS scores (at rest or after movement), PaCO2 values or postoperative spirometry. However, pain thresholds to pressure applied at the side of the chest contralateral to the site of incision decreased significantly from preoperative values on days 1 and 2 after surgery in both groups. The results of this study do not support the preoperative use of this combined regimen for post-thoracotomy pain.

Adult↗

Nitrous oxide in early labor. Safety and analgesic efficacy assessed by a double-blind, placebo-controlled study.

BACKGROUND: Intermittent self-administered nitrous oxide has long had widespread use as an analgesic in labor, but its efficacy has not been adequately established. Questions about its effect on maternal oxygenation between labor contractions also have been raised. METHODS: Twenty-six women were recruited to participate in a randomized, double-blind, cross-over, placebo-controlled study to assess the effect of intermittent nitrous oxide inhalation on labor pain and maternal hemoglobin oxygen saturation (SPO2) during the first stage of labor. Visual analog scale pain scores for each of five consecutive labor contractions were measured after administration of either nitrous oxide or compressed air. RESULTS: Mean visual analog scale pain scores for five contractions were 5.1, 5.2, 5.7, 5.2, and 5.6 (nitrous oxide) and 4.9, 5.2, 6.1, 5.6, and 5.7 (compressed air). There were no statistically significant differences in pain when nitrous oxide as compared with compressed air was administered. Pain scores did not differ significantly over time as a function of inhaled substance (F = 0.41, P = 0.53). The mean lowest SPO2 observed between these contractions after self-administration of nitrous oxide and air were 97, 97, 97, 97, and 97% (nitrous oxide) and 97, 96, 96, 96, and 96% (compressed air). SPO2 was significantly higher after nitrous oxide administration (F = 8.8, P = 0.007). CONCLUSION: While intermittent self-administered 50% nitrous oxide in oxygen does not appear to predispose parturient women to hemoglobin oxygen desaturation, its analgesic effect has yet to be clearly demonstrated.

Adult↗

A double-blind, placebo-controlled trial of transdermal fentanyl after abdominal hysterectomy. Analgesic, respiratory, and pharmacokinetic effects.

BACKGROUND: A randomized, double-blind, placebo-controlled trial was conducted to assess the analgesic, pharmacokinetic, and clinical respiratory effects of 72-h application of two transdermal fentanyl (TTSF) patch sizes in patients undergoing abdominal hysterectomy. METHODS: TTSF patches releasing 50 micrograms/h (TTSF-50) or 75 micrograms/h (TTSF-75) fentanyl or placebo patches were applied to 120 women 2 h before abdominal hysterectomy under general anesthesia. Postoperatively, all patients had access to supplemental morphine using patient-controlled analgesia pumps. Each patient was attended continuously by a research nurse for 8 h on the night before surgery and for 84 h after patch application. The following data were collected: visual analog scale pain scores, supplementary analgesia, fentanyl plasma concentration (4-h intervals), continuous hemoglobin saturation (pulse oximetry), respiratory pattern (continuous respiratory inductive plethysmography), and adverse effects (nausea, vomiting, pruritus). Data analysis included analysis of variance, Kruskal-Wallis, and chi-squared. P < 0.05 was considered significant. RESULTS: There were no demographic differences among groups. Visual analog scale pain scores were significantly lower for the TTSF-75 group, and supplemental morphine was significantly decreased in the TTSF-75 group in the postanesthesia care unit and for both the TTSF-50 and the TTSF-75 group for 8-48 h postoperatively. Between 5 and 36 h, the TTSF groups had significantly increased abnormal respiratory pattern including apneic episodes (tidal volume of less than 100 ml for more than 15 s) and episodes of slow respiratory rate (less than 8 breaths/min persisting for more than 5 min) and significantly increased requirement for oxygen supplementation. Nine patients in the TTSF groups were withdrawn because of severe respiratory depression compared to none in the placebo group. No significant between-group differences were present in the incidence of nausea, vomiting, or pruritus. Although fentanyl plasma concentration was higher in the TTSF-75 group than in the TTSF-50 group, the differences were not significant. Fentanyl plasma concentration decreased significantly 48 h after patch application. CONCLUSIONS: Application of TTSF patches 2 h preoperatively is associated with moderate supplementary opioid requirements for analgesia in the early postoperative period and ongoing opioid supplementation for at least 72 h. Although good analgesia is the result of this combination therapy, it is associated with a high incidence of respiratory depression requiring intensive monitoring oxygen supplementation, removal of the TTSF patches in approximately 11% of the patients and opioid reversal with naloxone in approximately 8% of the patients.

Administration, Cutaneous↗

Supplemental oxygen does not reduce myocardial ischemia in premedicated patients with critical coronary artery disease.

This randomized, prospective clinical study investigated the effects of supplemental inspired oxygen on arterial hemoglobin desaturation and myocardial ischemia in premedicated patients who have critical coronary artery stenosis, identified predictors for these adverse events, and examined the temporal relationship between hemoglobin desaturation and myocardial ischemia. Before elective coronary artery bypass surgery, 104 patients were monitored continuously by using a real-time electrocardiogram (V4 and V5 leads) recorder and a digital pulse oximeter. After a 2-h baseline monitoring period (Interval A), patients were given sublingual lorazepam 0.03 mg/kg, and were randomized to receive continuous supplemental inspired oxygen by nasal catheters [4 L/min (Oxygen Group, n = 52)] or to receive no supplemental inspired oxygen (Control Group, n = 52) (Interval B). One hour later, all patients received intramuscular morphine 0.15 mg/kg with perphenazine 0.05 mg/kg (Interval C). Interval C lasted 1 h, and the study was terminated. In the Oxygen Group, the incidence of desaturation was 25% before premedication and 11.5% after premedication (NS). In the Control Group after premedication, the incidence of desaturation increased from 25% to 56.9% (P < 0.001). There was no significant difference in the incidence of myocardial ischemia before or after premedication within or between the two groups. Arterial hemoglobin desaturation was not associated temporally with myocardial ischemia at any time. Predictors of desaturation after premedication included absence of supplemental O2, increased weight, age, and occurrence of desaturation before premedication. There were no identifiable predictors for myocardial ischemia after premedication. During Intervals A and C, episodes of hemoglobin desaturation were associated with small but statistically significant increases in mean heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Use of end-tidal PCO2 and transcutaneous PCO2 as noninvasive measurement of arterial PCO2 in extubated patients recovering from general anesthesia.

This study was designed to assess the accuracy of end-tidal PCO2 and transcutaneous PCO2 as measurements of arterial PCO2 in extubated, spontaneously breathing patients recovering from general anesthesia. In 30 patients, measurement of arterial transcutaneous, and end-tidal PCO2 were taken simultaneously with body temperature approximately every 15 minutes over a 2-hour period. Arterial PCO2 values were corrected for body temperature. Values for PaCO2 were compared with those for PETCO2 and PsCO2 by linear regression analysis and by calculation of bias +/- precision. Thirty-six percent of the capnogram tracings obtained did not develop a plateau phase. We found poor correlation between end-tidal and arterial PCO2 regardless of the shape of the capnogram tracing, as well as poor correlation between transcutaneous and arterial PCO2. Although the measurements of bias and precision of noninvasive PCO2 monitors in this population are comparable to studies in other populations, we advise caution in relying on the routine use of PETCO2 or PsCO2 for the noninvasive assessment of respiratory depression in extubated, spontaneously breathing patients recovering from general anesthesia.

Anesthesia, General↗

Preemptive analgesia. Clinical evidence of neuroplasticity contributing to postoperative pain.

Recent evidence suggests that surgical incision and other noxious perioperative events may induce prolonged changes in central neural function that later contribute to postoperative pain. The present study tested the hypothesis that patients receiving epidural fentanyl before incision would have less pain and need fewer analgesics post-operatively than patients receiving the same dose of epidural fentanyl after incision. Thirty patients (ASA physical status 2) scheduled for elective thoracic surgery through a posterolateral thoracotomy incision were randomized to one of two groups of equal size and prospectively studied in a double-blind manner. Epidural catheters were placed via the L2-L3 or L3-L4 interspaces preoperatively, and the position was confirmed with lidocaine. Group 1 received epidural fentanyl (4 micrograms/kg, in 20 ml normal saline) before surgical incision, followed by epidural normal saline (20 ml) infused 15 min after incision. Group 2 received epidural normal saline (20 ml) before surgical incision, followed by epidural fentanyl (4 micrograms/kg, in 20 ml normal saline) infused 15 min after incision. No additional analgesics were used before or during the operation. Anesthesia was induced with thiopental (3-5 mg/kg) and maintained with N2O/O2 and isoflurane. Paralysis was achieved with pancuronium (0.1 mg/kg). Postoperative analgesia consisted of patient-controlled intravenous morphine. Visual analogue scale pain scores were significantly less in group 1 (2.6 +/- 0.44) than in group 2 (4.7 +/- 0.58) 6 h after surgery (P less than 0.05), by which time plasma fentanyl concentrations had decreased to subtherapeutic levels (less than 0.15 ng/ml) in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia, Epidural↗

A randomized, double-blind comparison of lumbar epidural and intravenous fentanyl infusions for postthoracotomy pain relief. Analgesic, pharmacokinetic, and respiratory effects.

Although epidural opioids frequently are used to provide postoperative analgesia, several articles have suggested that the analgesia after epidural fentanyl is similar to that after an equal dose of fentanyl given intravenously. To address this issue further, 29 postthoracotomy patients were studied in a randomized, double-blinded trial comparing a lumbar epidural fentanyl infusion with an intravenous fentanyl infusion for analgesia, plasma fentanyl pharmacokinetics, and respiratory effects for 20 h postoperatively. In all patients in both groups, good analgesia was achieved (pain score less than 3, maximum 10) over a similar time course, although the patients receiving epidural infusion required a significantly larger fentanyl infusion dose than did the patients receiving intravenous infusion (group receiving epidural fentanyl infusion: 1.95 +/- 0.45 micrograms.kg-1.h-1; group receiving intravenous fentanyl infusion: 1.56 +/- 0.36 micrograms.kg-1.h-1; P = 0.0002). The time course for the plasma fentanyl concentrations was similar in the two groups, and plasma fentanyl concentrations were not significantly different at any sampling period (T7-T20; group receiving epidural fentanyl infusion: 1.8 +/- 0.5 ng/ml; group receiving intravenous fentanyl infusion: 1.6 +/- 0.6 ng/ml; P = 0.06). Similarly, calculated clearance values for the two groups were not significantly different (group receiving epidural fentanyl infusion: 0.95 +/- 0.26 l.kg-1.h-1; group receiving intravenous fentanyl infusion: 0.87 +/- 0.25 l.kg-1.h-1; P = 0.3). Both groups demonstrated a similar degree of mild to moderate respiratory depression postoperatively, which was assessed with continuous respiratory inductance plethysmography and sequential arterial blood gas analysis. Side effects (nausea, vomiting, pruritus) were mild and did not differ between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Hypoxaemia in adults in the post-anaesthesia care unit.

Continuous pulse oximetry was performed on 173 adults after general anaesthesia for elective inpatient surgery, throughout their post-anaesthesia care unit (PACU) stay. Supplemental oxygen was administered for greater than or equal to 30 min after arrival and subsequently discontinued before discharge to the ward. The mean and minimum oxyhaemoglobin saturation (SpO2) after discontinuing oxygen were lower than those values achieved during oxygen administration and preoperatively (P less than 0.001). At least one hypoxaemic episode (SpO2 less than or equal to 90% for greater than or equal to 15 sec) occurred in 70 subjects (41%) and 45 of these had a moderate-severe episode (SpO2 greater than or equal to 90% for less than or equal to 2 min or SpO2 less than or equal to 85%). The hypoxaemic episodes began 20 +/- 20 min (range 1-100; median 15) after discontinuing supplemental oxygen. Cyanosis was detected in only four of the 70 patients who desaturated. Factors associated with hypoxaemia were: ASA physical status class; surgical duration greater than or equal to 90 min; and preoperative mean SpO2 less than 95%. Factors not associated with hypoxaemia were: age, sex, % ideal body weight, smoking history, preoperative minimum SpO2, premedication and type of surgery. In conclusion, after discontinuing supplemental oxygen in the PACU, hypoxaemia was common, difficult to detect clinically, and associated with ASA class, surgical duration and preoperative mean SpO2.

Adult↗

A comparison of the analgesic and respiratory effects of epidural nalbuphine or morphine in postthoracotomy patients.

This randomized, double-blind study compared the analgesic and respiratory effects of lumbar epidural morphine 5 mg, nalbuphine 10 mg, and nalbuphine 20 mg in repeated doses in patients after thoracotomy; the first dose was administered intraoperatively. Pre-and postoperative monitoring included continuous pulse oximetry, respiratory inductance plethysmography, and repeated arterial blood gas analysis. Postoperatively, visual analogue pain scores, somnolence scores, respiratory rate, and arterial blood gases were determined for 16 h. Preoperatively, episodes of apnea were common during sleep but were not associated with low hemoglobin oxygen saturation or increased arterial carbon dioxide tension (PaCO2). During sleep, some otherwise normal patients had increased PaCO2, and 2 of 15 patients had episodes of hemoglobin oxygen saturation of less than 90%. Postoperatively, 1 and 2 h after arrival in the recovery room, patients who received morphine had lower pain scores than did those who received nalbuphine 10 or 20 mg (P less than 0.05). All 6 patients who received morphine had satisfactory analgesia. Two of 4 patients who received nalbuphine 10 mg and all 5 who received nalbuphine 20 mg were withdrawn from the study because of inadequate analgesia (morphine vs. nalbuphine 10 mg, not significant; morphine vs. nalbuphine 20 mg, P less than 0.01). Two patients who received morphine had persistently increased PaCO2 postoperatively. Two patients who received morphine had episodes of apnea and slow respiratory rate, which were most frequent 6 h after arrival in the recovery room. We conclude that lumbar epidural nalbuphine does not provide adequate analgesia after thoracotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Double-Blind Method↗

Lumbar epidural fentanyl infusions for post-thoracotomy patients: analgesic, respiratory, and pharmacokinetic effects.

Ten patients undergoing a thoracotomy were studied for 24 hours postoperatively to determine the effects of a continuous lumbar epidural fentanyl infusion on postoperative pain, arterial blood gases (ABG), respiratory pattern (respiratory inductive plethysmography, RIP), and fentanyl plasma concentration (CONC). Patients served as their own controls because RIP and ABG data were obtained the night prior to surgery during sleep. Epidural fentanyl was administered as a bolus of 1.5 micrograms/kg followed by an infusion of 1.0 micrograms/kg/h started 1 hour after induction. Insufficient analgesia was treated with a bolus of 0.5 micrograms/kg and an infusion increase of 0.25 micrograms/kg/h. Postoperative assessment included RIP, ABG, CONC, and visual analog pain score (PS). The average infusion rate postoperatively was 1.47 +/- 0.08 micrograms/kg/h (114.3 +/- 8.3 micrograms/h). A mean PS of 2.1 +/- 0.3 was achieved; however, there was a delay in attaining this. There was no significant incidence postoperatively of apnea or slow respiratory rate. A significant but clinically insubstantial increase in PaCO2 and decrease in pH occurred. A steady state CONC of approximately 2.0 ng/mL was reached after 9 hours. The PS correlated with CONC in half the patients (0.60 less than r less than 0.86), indicating a systemic component may have contributed to the analgesic effect.

Adult↗

A comparison of epidural and intramuscular morphine in patients following cesarean section.

This randomized, double-blind study compared epidural (EP) and intramuscular (IM) morphine in 24 healthy parturients for 24 h after cesarean section. The 11 EP subjects received 5 mg of EP morphine and normal saline intramuscularly, and the 13 IM patients received 5 mg of IM morphine and normal saline epidurally. Both injections were given simultaneously just after delivery and then upon request with at least 30 min between each pair of injections. Blood pressure, visual analogue scale pain score, somnolence score, and presence of nausea, vomiting, or pruritus were assessed every 30 min for 1 h after each dose and then hourly. Oxyhemoglobin saturation (Spo2) and respiratory rate (RR) and pattern were monitored continuously with pulse oximetry and respiratory inductive plethysmography. The EP group had significantly lower pain scores (less pain) than the IM (0.9 +/- 0.3 vs. 3.3 +/- 1.3; mean +/- SD; P less than 0.001) with less morphine (0.3 +/- 0.2 vs. 2.2 +/- 0.6 mg patient-1 h-1; P less than 0.001). There was no difference between groups for RR, Spo2, incidence or frequency of slow respiratory rate (SRR, 5-min mean RR less than 10) and apneas (AP, greater than or equal to 15 s of less than 100 ml tidal volume), incidence of nausea and/or vomiting, pruritus, or hypotension, and hours asleep or drowsy. There were no major respiratory abnormalities. During control monitoring of nine EP and 11 IM subjects while asleep postoperatively, the RR, Spo2, and incidence and frequency of SRR and AP were similar to the study period in both groups. In conclusion, EP morphine was a more effective analgesic than IM morphine, but the side effects of both were similar.

Adult↗

Epidural and intravenous fentanyl infusions are clinically equivalent after knee surgery.

The management of postoperative pain with continuous epidural fentanyl infusion was compared with continuous intravenous fentanyl infusion. In a randomized, doubleblind protocol we prospectively studied 20 patients undergoing repair of the anterior cruciate ligament of the knee. The quality of analgesia and the incidence of side effects were documented. Compared with patients receiving continuous intravenous fentanyl infusion, at 18 h postoperatively patients given continuous epidural fentanyl infusion reported similar pain scores both at rest (22 +/- 25 vs 27 +/- 21, P = 0.52) and with ambulation (59 +/- 18 vs 56 +/- 22, P = 0.82). Plasma fentanyl levels were 1.8 +/- 0.4 and 1.7 +/- 0.4 ng/mL (P = 0.91) for the intravenous and epidural groups, respectively. There were no significant differences in the incidence of nausea, pruritus, or urinary retention. There was no respiratory depression in either group. We conclude that when compared with continuous intravenous fentanyl infusion, continuous epidural fentanyl infusion offers no clinical advantages for the management of postoperative pain after knee surgery.

Adolescent↗