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Biomedical subjects

R S Sinatra

Publications and source records attributed to R S Sinatra.

At least 19 recordsLinked to original sources

Postoperative analgesia with parenteral opioids: does continuous delivery utilizing a transdermal opioid preparation affect analgesic efficacy or patient safety?

STUDY OBJECTIVES: To compare, in patients who underwent major orthopedic surgical procedures, the efficacy of intravenous (IV) patient-controlled analgesia (PCA) with morphine combined with continuous administration of two doses of fentanyl or placebo via transdermal therapeutic system with fentanyl (TTSF) patches. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: University teaching hospital. PATIENTS: 62 patients aged 18 to 65 years, presenting for elective orthopedic surgery and general anesthesia. INTERVENTIONS: Patients were randomized to one of three groups: group 1 received two placebo patches; group 2 received a 20 cm2 active patch delivering 50 micrograms/hr of fentanyl and a 30 cm2 placebo patch; group 3 received a 30 cm2 active patch delivering 75 micrograms/hr of fentanyl and a 20 cm2 placebo patch. All patches were placed approximately two hours prior to induction of general anesthesia. General anesthesia was induced with thiopental, intubation facilitated by the use of vecuronium or pancuronium, and anesthesia was maintained with isoflurane in an oxygen/nitrous oxide mixture (O2/N2O). Following surgery, IV morphine was provided using IV PCA with 1.5 mg of morphine with a 6-minute lockout and a 4-hour maximum dosage of 30 mg. MEASUREMENTS AND MAIN RESULTS: The time and dosage of morphine administered was recorded. Vital signs, pain intensity at rest, level of sedation, and arterial oxygen saturation (SpO2) were measured at intervals throughout the 72-hour study period and at 6 and 12 hours following patch removal. The presence of side effects was noted. Visual analog pain scores throughout the 72 hours of the study were not significantly different among groups. Patients receiving active TTSF required less IV PCA morphine at all time intervals. However, total opioid consumption was comparable among groups. The incidence of side effects was similar in all groups. CONCLUSIONS: There is no significant advantage to the routine use of continuous transdermal opioid delivery in patients receiving IV PCA after major orthopedic surgery.

Administration, Cutaneous↗

Patient-controlled analgesia with sufentanil: a comparison of two different methods of administration.

STUDY OBJECTIVE: To examine the safety and analgesic efficacy of sufentanil administered via either epidural or intravenous (i.v.) patient-controlled analgesia (PCA) in patients recovering from gynecologic surgery. DESIGN: Randomized, double-blind comparison. SETTING: Patient care unit at a university medical center. PATIENTS: 29 healthy women presenting for major intraabdominal gynecologic surgery with epidural anesthesia who requested postoperative PCA. INTERVENTIONS: Following completion of surgery performed using epidural anesthesia with 2% lidocaine and i.v sedation, patients were assigned to one of three treatment groups: Group 1-epidural PCA (EPCA) with sufentanil: 0.3 microgram/kg bolus followed by 8 micrograms/hr infusion plus epidural PCA boluses of 4 micrograms every 6 min as needed; Group 2-i.v. PCA with sufentanil: 0.3 microgram/kg bolus followed by 8 micrograms/hr infusion plus IV PCA boluses of 4 micrograms every 6 min as needed; or Group 3-i.v. PCA with morphine: 0.1 mg/kg bolus followed by 0.5 mg/hr infusion plus i.v. PCA boluses of 1 mg every 6 min as needed. MEASUREMENTS AND MAIN RESULTS: Patients were observed at regular intervals during a 24-hour evaluation period. Visual analog scale (VAS) scores were used to assess analgesia and satisfaction with therapy. Pulmonary function was assessed by monitoring respiratory rate, oxygen (O2) saturation, and forced expiratory flow. Total opioid dose delivered and the presence/severity of side effects was also collected. Sufentanil plasma levels were measured in a subset of eight patients. Patients receiving either EPCA or i.v. PCA sufentanil experienced equivalent analgesia that was more rapid in onset than i.v. PCA morphine. Total dose administered and plasma concentration of drug were similar in both sufentanil groups; however, a greater number of patients in the i.v. delivery group experienced clinically significant O2 desaturation. CONCLUSIONS: The main advantage of EPCA sufentanil in this postsurgical setting was its ability to provide a more rapid onset of analgesia than traditional i.v. PCA with morphine while offering greater safety than i.v. sufentanil.

Adult↗

A comparison of fentanyl, esmolol, and their combination for blunting the haemodynamic responses during rapid-sequence induction.

The purpose of this randomized, double-blind study was to compare the ability of a combination of fentanyl and esmolol to blunt the haemodynamic effects of intubation with that of either agent alone. Patients received fentanyl or saline four minutes before, and esmolol or saline two minutes before rapid-sequence induction of anaesthesia. The F2 group (n = 24) received fentanyl 2 micrograms.kg-1, the E2 group (n = 24) received esmolol 2 mg.kg-1, the F2/E2 group (n = 25) received a combination of fentanyl 2 micrograms.kg-1 and esmolol 2 mg.kg-1, and the F5 group (n = 26) received fentanyl 5 micrograms.kg-1. Following tracheal intubation, the maximum percent change from baseline heart rate was less in the F2/E2 and F5 groups (12% and 16% respectively) than in the E2 group (34%)(P < 0.05). The maximum percent changes from baseline systolic blood pressure in the F2/E2 and F5 groups (15% and 6% respectively) were less than in the F2 and E2 groups (24% and 33% respectively) (P < 0.05). The combination of a low dose of fentanyl and esmolol provides an alternative to a higher dose of fentanyl for blunting the haemodynamic responses to laryngoscopy and tracheal intubation during rapid-sequence induction in healthy patients.

Adrenergic beta-Antagonists↗

ST segment depression during labor and delivery.

ECG changes suggestive of myocardial ischemia are common during cesarean delivery under regional anesthesia. To determine the time course, duration, and significance of these ECG changes, we monitored 111 parturients with continuous ambulatory ECG (Holter) during and after cesarean delivery. Twenty-two parturients undergoing vaginal delivery were similarly monitored. ST segment depression was present in 25% of patients undergoing cesarean delivery but was not found in those patients delivering vaginally. ST segment elevation was not detected in either group. The incidence of ST segment depression during cesarean delivery was similar with epidural (29%), spinal (17%), and general (18%) anesthesia, occurring most commonly in the 30 min following delivery (P less than 0.001). Transthoracic echocardiographic imaging was performed in 23 patients undergoing cesarean section. Five of the 23 patients had seven episodes of intraoperative ST segment depression. Regional wall motion abnormalities were not present in any patient. A decrease in ejection fraction area greater than 15% from baseline or from previous interval ejection fraction area was present during four episodes of ST change. Three episodes of ST depression were not associated with significant decreases in ejection fraction area. Precordial Doppler monitoring for detection of venous air embolism in 25 patients revealed no association between the occurrence of venous air embolism and ST segment depression. We conclude that although significant myocardial impairment during cesarean delivery does not occur, episodes of ST depression may not all be merely an artifact of parturition.

Anesthesia, Conduction↗

Epidural fentanyl does not influence intravenous PCA requirements in the post-caesarean patient.

Forty ASA physical status I or II patients scheduled for elective Caesarean delivery were studied to determine the effect of epidural fentanyl on post-Caesarean delivery analgesic requirements as administered by intravenous patient-controlled analgesia (PCA). Following delivery of the infant, under epidural anaesthesia with lidocaine 2% with 1/200,000 epinephrine, patients were randomly assigned to receive either 10 ml of preservative-free normal saline via the epidural catheter or 100 micrograms of fentanyl with 8 ml preservative-free normal saline in a double-blinded fashion. On arrival in the post-anesthesia recovery room (PAR), patients were provided with intravenous PCA meperidine 12.5 mg every eight minutes as needed. Patients were visited at intervals over the next 24 hr to determine if any differences in narcotic requirements, demands for narcotics, or severity of pain were noted. No differences were observed in any values between the groups. It is concluded that a single bolus of epidural fentanyl does not provide an advantage for postoperative pain relief in this patient population.

Analgesia, Epidural↗

Comparison of epidurally administered sufentanil, morphine, and sufentanil-morphine combination for postoperative analgesia.

Postoperative analgesia provided by epidurally administered sufentanil and/or morphine was evaluated in 45 patients recovering from major gynecologic surgery. At the first complaint of pain in the Postanesthesia Care Unit, patients received a single epidural bolus of 30 micrograms sufentanil (group A), 5 mg morphine (group B), or 30 micrograms sufentanil plus 3 mg morphine (group C) in a randomized blinded fashion. Analgesic efficacy was assessed throughout the 24-h study period with 10-cm visual analog scales. The need for additional postoperative analgesia (patient-controlled analgesia, 1 mg of morphine every 6 min as necessary) and the incidence of adverse effects were also assessed. Patients receiving sufentanil (groups A and C) had significantly faster onset of analgesia than did patients given morphine alone (group B, P less than 0.05). Group B subjects experienced the longest duration of analgesia (B vs A and C, P less than 0.05) and required significantly less patient-controlled analgesia (morphine) than patients in group A (P less than 0.05). No patient developed clinically significant respiratory depression or excessive sedation, and there were no intergroup differences in incidence of pruritus or nausea (P value not significant). The data indicate that a mixture of sufentanil and morphine provides either a more rapid onset of epidural analgesia or reduced patient-controlled analgesia narcotic requirement than respective doses of each agent administered alone.

Adult↗

Nausea prophylaxis using transdermal scopolamine in the setting of patient-controlled analgesia.

We evaluated the effectiveness of transdermal scopolamine in patients receiving morphine via patient-controlled intravenous analgesia following intra-abdominal gynecologic surgery. Soon after arrival in the post-anesthesia recovery unit (time 0), patients were randomized either to receive or not receive a postauricular transdermal scopolamine patch. Nausea and vomiting were scored on a 0-3 scale at this time and at 2, 4, 6, and 24 hours. Patients were treated with droperidol as deemed necessary by the primary care nurse. Within 2-4 hours, transdermal scopolamine patients evidenced less nausea and vomiting and required less droperidol than their counterparts who did not receive transdermal scopolamine. A significant decline in the severity of nausea was noted in the transdermal scopolamine group between 2-24 hours; significant inter-group differences were noted for changes in nausea severity during the 0-6-hour and 0-24-hour intervals. Transdermal scopolamine patients evidenced a significant (P less than .05) decrease in the severity of vomiting during the first 2 hours, significantly different from the increase in the non-transdermal scopolamine patients. After the 4-hour assessment, no transdermal scopolamine patients required droperidol; nine doses were administered to the patients who were not given transdermal scopolamine (P less than .05). Thus, transdermal scopolamine therapy appears to be an effective means of treating the nausea and vomiting that are encountered after gynecologic surgery.

Administration, Cutaneous↗

Exogenous opioids in human breast milk and acute neonatal neurobehavior: a preliminary study.

Opioid analgesia requirements, distribution into breast milk, and influence on neonatal neurobehavior were evaluated in ten parturient-neonate pairs nursing after elective cesarean section during epidural anesthesia. Five patients received first a loading dose of intravenous meperidine after umbilical cord clamping, then patient-controlled analgesia (PCA) with intravenous meperidine, and finally meperidine tablets as needed. Five patients received morphine in the same manner. Treatment groups showed no differences with respect to neonatal Apgar scores or visual analog scale (VAS) pain or satisfaction scores at 24 and 48 h postpartum. Breast milk specimens, obtained at 12, 24, 36, 48, 72, and 96 h postpartum and analyzed for opioids and metabolites, showed persistently elevated normeperidine concentrations in the meperidine group. A blinded psychologist evaluated each infant once on the 3rd day of life with the Brazelton Neonatal Behavioral Assessment Scale (NBAS). A priori, the "alertness" and three "human orientation" outcomes of the NBAS were chosen for analysis as best measures of opioid-induced effects. On all four outcomes, neonates in the morphine group scored significantly higher (P less than 0.05) than neonates in the meperidine group. We conclude that post-cesarean delivery PCA with morphine provides equivalent maternal analgesia and overall satisfaction as that provided by PCA with meperidine, but with significantly less neurobehavioral depression among breast-fed neonates on the 3rd day of life.

Analgesia, Obstetrical↗

A comparison of oxymorphone and fentanyl as narcotic supplements in general anesthesia.

The safety and efficacy of two potent opiate analgesics, fentanyl and oxymorphone, used as adjuncts in general anesthesia, were studied in 39 patients undergoing elective gynecologic surgery of at least 2 hours duration. Based on a potency ratio of 10:1, patients received either fentanyl 6.5 micrograms/kg or oxymorphone 65 micrograms/kg prior to a thiopental 2 to 3 mg/kg succinylcholine induction and endotracheal intubation. Additional maintenance narcotic and isoflurane were administered as required by the "blinded" anesthesiologist in response to hemodynamic alterations 15% above a presurgical baseline. Overall analysis included hemodynamic response at preset intraoperative intervals, total anesthetic requirements, and stability of vital signs in the recovery room. Blood pressure and heart rate were reliably controlled with either agent; however, less narcotic (ml) and recovery room analgesics were required in the oxymorphone-treated group (p less than 0.05). Decreased naloxone requirements (p less than 0.05) and a more rapid emergence suggested that fentanyl was a safer agent when administered in relatively unrestricted fashion.

Anesthesia, General↗

A comparison of morphine, meperidine, and oxymorphone as utilized in patient-controlled analgesia following cesarean delivery.

Seventy-five patients (n = 75) undergoing elective cesarean delivery during epidural anesthesia were randomly assigned to receive one of three opioid analgesics via patient-controlled analgesia (PCA) when they first complained of pain in the recovery room. Following administration of an analgesic loading dose, patients were allowed to self-administer morphine 1.8 mg, meperidine 18 mg, or oxymorphone 0.3 mg iv every 8 min as required. Data collected during the 24-h observation period included visual analog scale (VAS) pain scores at rest and during movement, VAS patient satisfaction scores, total drug administered, the ratio of attempts/injections, and the incidence of nausea/vomiting, sedation, and pruritus. After adjusting for narcotic potency, no differences in 24-h dose requirements were noted between treatment groups (NS). All patients achieved an excellent level of analgesia at rest (NS); however, onset was most rapid with oxymorphone (P less than 0.05). The percentage of patients reporting severe pain during movement was highest in the meperidine group (P less than 0.05). Oxymorphone was associated with the highest incidence of nausea and vomiting (P less than 0.05), whereas increased sedation and pruritus were noted with morphine. Patient satisfaction with drug effect demonstrated significant negative correlations with resting pain scores and degree of sedation. Whereas morphine is a more commonly utilized PCA analgesic, the excellent analgesia, low incidence of sedation, and high patient satisfaction provided by meperidine and oxymorphone suggested useful alternatives.

Adult↗

Spinal cord distribution of 3H-morphine after intrathecal administration: relationship to analgesia.

The distribution of intrathecally administered 3H-morphine was examined by light microscopic autoradiography in rat spinal cord and temporal changes in silver grain localization were compared with results obtained from simultaneous measurements of analgesia. After tissue processing, radio-activity was found to have penetrated in superficial as well as in deeper layers (Rexed lamina V, VII, and X) of rat spinal cord within minutes after application. Silver grain density reached maximal values at 30 min in every region of cord studied. Radioactivity decreased rapidly between 30 min and 2 hr and then more slowly over the next 24 hr. In rats tested for responses to a thermal stimulus (tail flick test), intrathecal administration of morphine (5 and 15 micrograms) resulted in significant dose dependent analgesia that peaked at 30 min and lasted up to 5 hr (P less than 0.5). There was a close relationship between analgesia and spinal cord silver grain density during the first 4 hr of the study. It is postulated that the onset of spinal morphine analgesia depends on appearance of molecules at sites of action followed by the activation of anti-nociceptive mechanisms.

Analgesia↗

Internodal distribution of phosphatidylcholine biosynthetic activity in teased peripheral nerve fibres: an autoradiographic study.

Radioactive choline injected into mouse sciatic nerve is rapidly incorporated into into phosphatidylcholine. Sites of deposition of this phospholipid have been localized along the internode in autoradiography prepared from individually teased fibres. The newly synthesized lecithin formed during 20 min or 2 h labelling periods is concentrated in the perinuclear region of the Schwann cell and in strands radiating from this portion of the cell. This labelling pattern, representing a complex of enzyme activities, is distributed in a similar, though not identical, fashion to that of Schwann cell mitochondria as localized by histochemical methods. These findings suggest that soluble and membrane-associated enzymes required for phosphatidylcholine formation are distributed in Schwann cell cytoplasm along superficial longitudinally oriented channels as depicted in recent freeze-fracture studies.

Animals↗

The effects of acute and chronic morphine treatment on the process of facial nerve regeneration.

Prominent cellular responses to axonal interruption include enhanced synthesis of RNA and protein in the neuronal perikaryon, and proliferation of reactive Schwann cells. Since morphine has been shown to significantly depress cellular metabolism, we examined its effect on these and other reparative responses underlying nerve fiber regeneration. Rat facial nerve trunks from saline, acute morphine, and continuous morphine-treated animals were examined by light and electron microscopy at 3, 7 and 14 days after crush injury. The number of axonal sprouts/unit area and the diameters of regenerating axons were quantified at each survival interval. Both saline-treated and acute morphine-treated facial nerves demonstrated myelin degradation and Schwann cell hypertrophy (at 3 days post-axotomy), sprout outgrowth (at 7 days) and axon maturation and myelination (at 14 days). In the chronic morphine-treated animals, a retardation of the regenerative process was evident. Axon sprout outgrowth and axonal diameters were reduced at 3 and 7 days post-axotomy. In treated 14-day animals, axon diameters were normal; however, significantly fewer axon profiles/unit area were observed. After chronic morphine exposure, Schwann cell hypertrophy and proliferation, as well as myelin debris removal, were inhibited at all survival periods.

Animals↗