Biomedical subjects

A R Bjorksten

Publications and source records attributed to A R Bjorksten.

At least 19 recordsLinked to original sources

PubMed2004

N-acetylcysteine enhances muscle cysteine and glutathione availability and attenuates fatigue during prolonged exercise in endurance-trained individuals.

The production of reactive oxygen species in skeletal muscle is linked with muscle fatigue. This study investigated the effects of the antioxidant compound N-acetylcysteine (NAC) on muscle cysteine, cystine, and glutathione and on time to fatigue during prolonged, submaximal exercise in endurance athletes. Eight men completed a double-blind, crossover study, receiving NAC or placebo before and during cycling for 45 min at 71% peak oxygen consumption (VO2 peak) and then to fatigue at 92% VO2 peak. NAC was intravenously infused at 125 mg.kg(-1).h(-1) for 15 min and then at 25 mg.kg(-1).h(-1) for 20 min before and throughout exercise. Arterialized venous blood was analyzed for NAC, glutathione status, and cysteine concentration. A vastus lateralis biopsy was taken preinfusion, at 45 min of exercise, and at fatigue and was analyzed for NAC, total glutathione (TGSH), reduced glutathione (GSH), cysteine, and cystine. Time to fatigue at 92% VO2 peak was reproducible in preliminary trials (coefficient of variation 5.6 +/- 0.6%) and with NAC was enhanced by 26.3 +/- 9.1% (NAC 6.4 +/- 0.6 min vs. Con 5.3 +/- 0.7 min; P <0.05). NAC increased muscle total and reduced NAC at both 45 min and fatigue (P <0.005). Muscle cysteine and cystine were unchanged during Con, but were elevated above preinfusion levels with NAC (P <0.001). Muscle TGSH (P <0.05) declined and muscle GSH tended to decline (P=0.06) during exercise. Both were greater with NAC (P <0.05). Neither exercise nor NAC affected whole blood TGSH. Whereas blood GSH was decreased and calculated oxidized glutathione increased with exercise (P <0.05), both were unaffected by NAC. In conclusion, NAC improved performance in well-trained individuals, with enhanced muscle cysteine and GSH availability a likely mechanism.

Acetylcysteine↗

PubMed2004

Pethidine and skin warming to prevent shivering during endovascular cooling.

We tested the efficacy of pethidine and cutaneous warming to prevent shivering during percutaneous cooling in unanaesthetized patients. Ten patients scheduled for cranial neurosurgery received pethidine infusion and skin warming. The Setpoint internal heat-exchanging catheter was inserted and cooling to 33.5 degrees C was started. Clonidine and chlorpromazine were given as "rescue medication" to treat shivering. General anaesthesia was planned to be induced after cooling was complete. Rewarming was initiated at dural closure. Three patients successfully completed the protocol, cooling to 33.8 degrees C at a median rate of 3.6 (range: 3.4-3.8) degrees C/h. Two patients cooled to 33.8 degrees C but required treatment for shivering (cooling rate: 2.9 [2.8-3.1] degrees C/h). Four patients failed to cool adequately because of refractory shivering (cooling rate: 20 [1.5-2.9] degrees C/h). One patient did not shiver and yet failed to cool adequately (cooling rate: 0.76 degrees C/h). Rewarming was at a rate of 26 (1.2-4.3) degrees C/h. There were no significant complications arising from catheter placement. The combination of skin warming and pethidine was not reliable enough to be recommended for use during endovascular cooling in unanaesthetized patients.

Adult↗

PubMed2004

Comparison of disposable and reusable laryngeal mask airways in spontaneously ventilating adult patients.

Recent studies have indicated that despite stringent sterilization processes, the reusable silicone laryngeal mask airway (LMA) has the potential for disease transmission through residual biological debris. As a result, a polyvinyl chloride (PVC) disposable LMA has been introduced. This randomized trial involved 138 spontaneously ventilating adult patients who underwent elective surgery requiring airway management with an LMA to determine whether there is a clinical difference between the disposable Portex LMA (PLMA) and the standard reusable LMA in terms of ease of insertion, intra-operative cuff pressures and postoperative incidence of sore throat. There was no significant difference in first attempt insertion success rates (79% vs 84%) or difference in the incidence of postoperative sore throat observed between the two groups. Cuff pressure increases with nitrous oxide anaesthesia were significantly larger with the reusable LMA. The disposable PLMA provided a suitable airway in spontaneously ventilating patients without the risk of disease transmission inherent in a reusable device.

Anesthesia, General↗

PubMed2003

A new system to target the effect-site during propofol sedation.

BACKGROUND: We evaluated a new, integrated, covariate-adjusted, target-controlled infusion system during sedation with propofol combined with 50% nitrous oxide (N2O) and with propofol only (Air). METHODS: The protocol consisted of sequential 15-minute cycles in 20 volunteers. After a 15-minute control period, propofol was infused to an initial target effect-site concentration of 0.25 microg x ml-1 (N2O) or 1.5 microg x ml-1 (Air). Subsequently, the target effect-site concentration was increased by 0.25 (N2O) or 0.5 microg x ml-1 (Air) for 15 min This sequence was continued until the volunteers lost consciousness as defined by an Observer's Assessment Alertness/Sedation (OAA/S) score = 2. RESULTS: Venous plasma propofol concentrations at the beginning(9 elapsed minutes) and end(15 elapsed minutes) of the pseudo-steady state period differed by only 0.00 +/- 0.16 microg x ml-1 (P = 0.78) during the N2O and 0.00 +/- 0.25 microg x ml-1 (P = 0.91) during the Air trial. OAA/S scores and bispectral index values, as surrogate measures of pharmacodynamic effect, were not different during this time in either trial. The median(25th, 75th percentiles) of the median performance error (%) was -13 (-24, -1) during the N2O and -18 (-26, -9) during the Air trial. The median absolute performance error (%) was 17 (10, 24) in the N2O and 22 (12, 28) in Air trial. The divergence (%/h) was -10 (-26, 4) in the N2O and 14 (-21, 26) in Air trial. The wobble was 7 (5, 10) in the N2O and 6 (4, 8) in the Air trial. CONCLUSIONS: When tested with venous blood samples, our TCI system for propofol, using a covariate-adjusted, integrated pharmacokinetic model to target effect-site concentrations, demonstrated a clinically acceptable accuracy and stability during mild to moderate sedation.

Adult↗

PubMed2003

Automated responsiveness test and bispectral index monitoring during propofol and propofol/N2O sedation.

BACKGROUND: Sedation practice, especially when non-anaesthesia personnel are involved, requires efficient anaesthetic depth monitoring. Therefore, we used prediction probability (PK) to evaluate the performance of the bispectral index (BIS) of the EEG and automated responsiveness test (ART) to predict sedation depth and loss of subject's responsiveness during propofol sedation, with and without N2O. METHODS: Twenty volunteers were studied during propofol administration with (N2O) and without (Air) N2O. The protocol consisted of sequential 15-min cycles. After a control period, propofol was infused to a target effect-site concentration of 0.25 microg/ml (N2O) or 1.5 microg/ml (Air), which was subsequently increased by 0.25 or 0.5 microg/ml, respectively, until loss of responsiveness was detected by loss of response to command [observer's assessment of alertness/sedation (OAA/S) score <or= 2]. RESULTS: Deeply sedated patients did not respond to ART indicating that the sensitivity was 1.0 with or without N2O. The specificity of ART was 0.24 with Air and 0.98 with N2O. The BIS was better than ART in predicting OAA/S score (PK = 0.84 vs. 0.77) and loss of responsiveness (PK = 0.87 vs. 0.69) during the Air trial. Nitrous oxide decreased the performance of BIS in predicting OAA/S score (PK = 0.76), but increased the performance of ART to predict loss of responsiveness (PK = 0.85). CONCLUSION: BIS and ART comparably predict sedation and loss of responsiveness. However, ART, because of its resistance to false-normal responses, might prove to be more useful on an individual patient basis - especially in the presence of agents that impair BIS sensitivity.

Adult↗

PubMed2003

Alfentanil infusion as a component of intravenous anaesthesia for coronary artery bypass surgery with "fast-track" recovery.

Alfentanil and propofol total intravenous anaesthesia was assessed in 25 patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass (CPB). A manually controlled alfentanil infusion, calculated from estimated lean body mass and published pharmacokinetic data, was effective in achieving target plasma concentrations, while the "Diprifusor" system was used to vary propofol target concentrations according to changes in haemodynamics and anaesthetic requirement. The effects of CPB on alfentanil plasma concentrations were offset by changes in protein binding and free-fraction of the drug. With the use of only two target plasma concentrations for alfentanil (changed after CPB), a pre-determined infusion profile ensured effective plasma concentrations during surgery and concentrations unlikely to inhibit extubation within six hours of sternal closure.

Alfentanil↗

PubMed2002

N-acetylcysteine infusion alters blood redox status but not time to fatigue during intense exercise in humans.

Infusion of the antioxidant N-acetylcysteine (NAC) reduces fatigability in electrically evoked human muscle contraction, but due to reported adverse reactions, no studies have investigated NAC infusion effects during voluntary exercise in humans. We investigated whether a modified NAC-infusion protocol (125 mg. kg(-1). h(-1) for 15 min, then 25 mg. kg(-1). h(-1)) altered blood redox status and enhanced performance during intense, intermittent exercise. Eight untrained men participated in a counterbalanced, double-blind, crossover study in which they received NAC or saline (control) before and during cycling exercise, which comprised three 45-s bouts and a fourth bout that continued to fatigue, at 130% peak oxygen consumption. Arterialized venous blood was analyzed for glutathione status, hematology, and plasma electrolytes. NAC infusion induced no severe adverse reactions. Exercise decreased the reduced glutathione (P < 0.005) and increased oxidized glutathione concentrations (P < 0.005); NAC attenuated both effects (P < 0.05). NAC increased the rise in plasma K(+) concentration-to-work ratio (P < 0.05), indicating impaired K(+) regulation, although time to fatigue was unchanged (NAC 102 +/- 45 s; saline 107 +/- 53 s). Thus NAC infusion altered blood redox status during intense, intermittent exercise but did not attenuate fatigue.

Acetylcysteine↗

PubMed2002

Determination of remifentanil in human blood by capillary gas chromatography with nitrogen-selective detection.

A validated method for the determination of remifentanil in human blood, applicable to all therapeutic concentrations, using capillary GC with nitrogen-specific detection and fentanyl as the internal standard has been developed. Citrated whole blood samples were extracted into 1-chlorobutane following precipitation of proteins with methanol. The drugs were back extracted into 10 mM HCl and re-extracted into methanol-1-chlorobutane. The extracts were reconstituted in methanol and injected onto a 25-m BPX-5 column. The lower limit of quantitation was 0.2 ng/ml with within- and between-day coefficients of variation of less than 15%.

Analgesics, Opioid↗

PubMed2002

Remifentanil concentration during target-controlled infusion of propofol.

After institutional approval and with written informed consent, eight surgical patients were infused intravenously with remifentanil at 250 ngkg lean body mass (LBM)(-1) x min(-1) for 30 min. Cardiovascular and respiratory parameters were recorded and arterial blood samples were taken at regular intervals. In each patient, the same protocol was repeated 40 min later during propofol infused to a target concentration of 3.0 microg x ml(-1). Blood concentrations of remifentanil and propofol were assayed using capillary gas chromatography and high performance liquid chromatography techniques respectively. The number of subjects enrolled was determined by testing the successive areas under the remifentanil time-concentration curve (AUC) for significant difference or non-difference using sequential analysis. The median measured propofol concentration was 3.5 (range: 2.6-4.5) microg x ml(-1) which did not change significantly during the second remifentanil infusion. The median AUC during propofol infusion was greater than control in all subjects, although there was considerable variation of 94.4 (64.3-129.6) versus 64.6 (34.8-126.9) ng x ml(-1) x min; P=0.008, n=8. After 30 min, there was no significant difference in remifentanil concentration during propofol infusion when compared with remifentanil alone of 4.6 (3.2-5.7) versus 3.8 (1.6-4.9) ng x ml(-1); P=0.73, n=8. Co-administration of propofol and remifentanil may result in greater remifentanil concentrations than when remifentanil is infused alone.

Adolescent↗

PubMed2001

Neither nalbuphine nor atropine possess special antishivering activity.

The special antishivering action of meperidine may be mediated by its kappa or anticholinergic actions. We therefore tested the hypotheses that nalbuphine or atropine decreases the shivering threshold more than the vasoconstriction threshold. Eight volunteers were each evaluated on four separate study days: 1) control (no drug), 2) small-dose nalbuphine (0.2 microg/mL), 3) large-dose nalbuphine (0.4 microg/mL), and 4) atropine (1-mg bolus and 0.5 mg/h). Body temperature was increased until the patient sweated and then decreased until the patient shivered. Nalbuphine produced concentration-dependent decreases (mean +/- SD) in the sweating (-2.5 +/- 1.7 degrees C. microg(-1). mL; r(2) = 0.75 +/- 0.25), vasoconstriction (-2.6 +/- 1.7 degrees C. microg(-1). mL; r(2) = 0.75 +/- 0.25), and shivering (-2.8 +/- 1.7 degrees C. microg(-1). mL; r(2) = 0.79 +/- 0.23) thresholds. Atropine significantly increased the thresholds for sweating (1.0 degrees C +/- 0.4 degrees C), vasoconstriction (0.9 degrees C +/- 0.3 degrees C), and shivering (0.7 degrees C +/- 0.3 degrees C). Nalbuphine reduced the vasoconstriction and shivering thresholds comparably. This differs markedly from meperidine, which impairs shivering twice as much as vasoconstriction. Atropine increased all thresholds and would thus be expected to facilitate shivering. Our results thus fail to support the theory that activation of kappa-opioid or central anticholinergic receptors contribute to meperidine's special antishivering action.

Adult↗

PubMed2001

Buspirone and meperidine synergistically reduce the shivering threshold.

UNLABELLED: Mild hypothermia (i.e., 34 degrees C) may prove therapeutic for patients with stroke, but it usually provokes shivering. We tested the hypothesis that the combination of buspirone (a serotonin 1A partial agonist) and meperidine synergistically reduces the shivering threshold (triggering tympanic membrane temperature) to at least 34 degrees C while producing little sedation or respiratory depression. Eight volunteers each participated on four randomly-assigned days: 1) large-dose oral buspirone (60 mg); 2) large-dose IV meperidine (target plasma concentration of 0.8 microg/mL); 3) the combination of buspirone (30 mg) and meperidine (0.4 microg/mL); and 4) a control day without drugs. Core hypothermia was induced by infusion of lactated Ringer's solution at 4 degrees C. The control shivering threshold was 35.7 degrees C +/- 0.2 degrees C. The threshold was 35.0 degrees C +/- 0.8 degrees C during large-dose buspirone and 33.4 degrees C +/- 0.3 degrees C during large-dose meperidine. The threshold during the combination of the two drugs was 33.4 degrees C +/- 0.7 degrees C. There was minimal sedation on the buspirone and combination days and mild sedation on the large-dose meperidine day. End-tidal PCO2 increased approximately 10 mm Hg with meperidine alone. Buspirone alone slightly reduced the shivering threshold. The combination of small-dose buspirone and small-dose meperidine acted synergistically to reduce the shivering threshold while causing little sedation or respiratory toxicity. IMPLICATIONS: Mild hypothermia may be an effective treatment for acute stroke, but it usually triggers shivering, which could be harmful. Our results indicate that the combination of small-dose buspirone and small-dose meperidine acts synergistically to reduce the shivering threshold while causing little sedation or respiratory toxicity. This combination may facilitate the induction of therapeutic hypothermia in stroke victims.

Adult↗

PubMed2001

Opioids inhibit febrile responses in humans, whereas epidural analgesia does not: an explanation for hyperthermia during epidural analgesia.

BACKGROUND: Epidural analgesia is frequently associated with hyperthermia during labor and in the postoperative period. The conventional assumption is that hyperthermia is caused by the technique, although no convincing mechanism has been proposed. However, pain in the "control" patients is inevitably treated with opioids, which themselves attenuate fever. Fever associated with infection or tissue injury may then be suppressed by opioids in the "control" patients while being expressed normally in patients given epidural analgesia. The authors therefore tested the hypothesis that fever in humans is manifested normally during epidural analgesia, but is suppressed by low-dose intravenous opioid. METHODS: The authors studied eight volunteers, each on four study days. Fever was induced each day by 150 IU/g intravenous interleukin 2. Volunteers were randomly assigned to: (1) a control day when no opioid or epidural analgesia was given; (2) epidural analgesia using ropivacaine alone; (3) epidural analgesia using ropivacaine in combination with 2 microg/ml fentanyl; or (4) intravenous fentanyl at a target plasma concentration of 2.5 ng/ml. RESULTS: Fentanyl halved the febrile response to pyrogen, decreasing integrated core temperature from 7.0 +/- 3.2 degrees C. h on the control day, to 3.8 +/- 3.0 degrees C. h on the intravenous fentanyl day. In contrast, epidural ropivacaine and epidural ropivacaine-fentanyl did not inhibit fever. The fraction of core-temperature measurements that exceeded 38 degrees C was halved by intravenous fentanyl, and the fraction exceeding 38.5 degrees C was reduced more than fivefold. CONCLUSIONS: These data support the authors' proposed mechanism for hyperthermia during epidural analgesia. Fever during epidural analgesia should thus not be considered a complication of the anesthetic technique per se.

Adult↗

PubMed2001

Automated responsiveness test (ART) predicts loss of consciousness and adverse physiologic responses during propofol conscious sedation.

BACKGROUND: The authors evaluated a device designed to provide conscious sedation with propofol (propofol-air), or propofol combined with 50% nitrous oxide (N2O; propofol-N2O). An element of this device is the automated responsiveness test (ART), a method for confirming that patients remain conscious. The authors tested the hypotheses that the ART predicts loss of consciousness and that failure to respond to the ART precedes sedation-induced respiratory or hemodynamic toxicity. METHODS: The protocol consisted of sequential 15-min cycles in 20 volunteers. After a 15-min control period, propofol was infused to an initial target effect-site concentration of 0.0 microg/ml with N2O or 1.5 microg/ml with air. Subsequently, the propofol target effect-site concentration was increased by a designated increment (0.25 and 0.5 microg/ml) and the process repeated. This sequence was continued until loss of consciousness, as defined by an Observer's Assessment of Alertness/Sedation (OAA/S) score of 10/20 or less, or until an adverse physiologic event was detected. RESULTS: The OAA/S score at which only 50% of the volunteers were able to respond to the ART (P50) during propofol-N2O was 11.1 of 20 (95% confidence interval [CI]: 10.6-11.8); the analogous P50 was 11.8 of 20 (95% CI: 11.4-12.3) with propofol-air. Failure to respond to the ART occurred at a plasma propofol concentration of 0.7 +/- 0.6 microg/ml with propofol-N2O and 1.6 +/- 0.6 microg/ml with propofol-air, whereas loss of consciousness occurred at 1.2 +/- 0.8 microg/ml and 1.9 +/- 0.7 microg/ml, respectively. There were no false-normal ART responses. CONCLUSION: The ART can guide individual titration of propofol because failure to respond to responsiveness testing precedes loss of consciousness and is not susceptible to false-normal responses. The use of N2O with propofol for conscious sedation decreases the predictive accuracy of the ART.

Adult↗

PubMed2000

Alfentanil reduces the febrile response to interleukin-2 in humans.

OBJECTIVE: Manifestation of intraoperative fever is impaired by volatile anesthetics and muscle relaxants. Opioids are common anesthetic adjuvants and remain the dominant treatment for postoperative surgical pain and sedation of critically ill patients. The effect of opioids on normal thermoregulatory control is well established. However, the extent to which these drugs might inhibit fever remains unknown. Accordingly, we tested the hypothesis that relatively low plasma concentrations of the mu-receptor agonist alfentanil reduce fever magnitude. DESIGN: Prospective, randomized, crossover study. SETTING: Outcomes Research Laboratory, at the Department of Anesthesia and Perioperative Care, University of California, San Francisco. PATIENTS: Eight healthy male volunteers, aged 25-31 yrs, each studied on three separate days. INTERVENTION: Each volunteer was given an intravenous injection of 30 IU/g interleukin (IL)-2, followed 2 hrs later by 70 IU/g. One hour after the second dose, the volunteers were randomly assigned to three doses of alfentanil: a) none (control); b) a target plasma concentration of 100 ng/mL; and c) a target concentration of 200 ng/mL. Opioid administration continued for 5 hrs. METHODS AND MAIN RESULTS: Alfentanil significantly reduced the febrile response to pyrogen, decreasing integrated tympanic membrane temperatures from 7.5+/-2.2 degrees C x hr on the control day, to 4.9+/-1.5 degrees C x hr with 100 ng/mL alfentanil, and to 5.1+/-1.7 degrees C x hr with 200 ng/mL alfentanil (p = .011). Peak temperatures were also significantly reduced from 38.5+/-0.4 degrees C on the control day, to 38.0+/-0.4 degrees C on the 100 ng/mL-alfentanil day and 38.0+/-0.6 degrees C on the 200-ng/mL day (p = .019). Plasma cytokine concentrations increased after IL-2 administration, roughly in proportion to the elevation in core temperature. However, cytokine concentrations did not differ significantly among the treatment groups. CONCLUSION: Alfentanil significantly reduced the febrile response to IL-2 administration. However, the reduction was comparable at plasma concentrations near 100 and 200 ng/mL. These data indicate that concentrations of opioids commonly observed in critical care patients significantly inhibit the manifestation of fever.

Adult↗

PubMed1999

The effects of physical treatment on induced fever in humans.

PURPOSE: Initial treatments for fever include the amelioration of underlying causes and administration of antipyretic medications. However, patients who fail these treatments are often actively cooled, which may be counterproductive because decreasing skin temperature increases the thermoregulatory core target temperature. Cooling may also provoke metabolic and autonomic stress and thermal discomfort. SUBJECTS AND METHODS: We studied 9 subjects, each on 3 days. Fever was induced each day with 100,000 IU/kg of interleukin-2 administered intravenously (elapsed time zero). Randomly assigned treatments were 1) control (a cotton blanket), 2) cooling (forced air at 15 degrees C), or 3) self-adjust (forced-air warming adjusted to comfort). Treatments were maintained for 3 to 8 elapsed hours. RESULTS: Peak core temperatures (mean +/- SD) were 38.4 +/- 0.5 degrees C on the control day, 38.1 +/- 0.5 degrees C on the cooling day, and 38.5 +/- 0.4 degrees C on the self-adjust day. Integrated core temperatures were 6.0 +/- 1.6 degrees C x h on the control day, 5.7 +/- 2.2 degrees C x h on the cooling day, and 6.4 +/- 1.2 degrees C x h on the self-adjust day. Neither peak nor integrated core temperatures differed significantly on the 3 days. Shivering was common on the cooling day but otherwise rare. Oxygen consumption was normal on the control and self-adjust days but increased 35% to 40% during cooling (P = 0.0001). Mean arterial pressure and plasma norepinephrine and epinephrine concentrations were significantly greater during cooling (P <0.05). On a self-reported thermal comfort scale, the subjects were miserable during cooling and significantly more comfortable on the self-adjust than control day (P <0.05). CONCLUSION: We conclude that active cooling should be avoided in unsedated patients with moderate fever, because it does not reduce core temperature but does increase metabolic rate, activate the autonomic nervous system, and provoke thermal discomfort.

Adult↗

PubMed1999

Exercise hemodynamic performance of the pulmonary autograft following the Ross procedure.

BACKGROUND AND AIMS OF THE STUDY: The Ross procedure, in which the aortic valve is replaced with the patient's own pulmonary valve (pulmonary autograft), is considered an excellent alternative for younger patients requiring elective aortic valve replacement. Although resting pulmonary autograft hemodynamics are excellent, exercise hemodynamic data are lacking. The study aim was to measure the hemodynamic performance of the pulmonary autograft with exercise Doppler echocardiography (DE). METHODS: Twenty-four Ross procedure patients (20 males, four females; mean age 46 +/- 11 years) were studied at 25 +/- 14 months after aortic valve replacement with a pulmonary autograft. Patients had baseline supine DE to measure the maximum velocity (Vmax), and the peak and mean pressure gradient across the pulmonary autograft. Effective orifice area was calculated from the continuity equation and indexed to body surface area (EOAi). Patients then underwent symptom-limited upright bicycle exercise with supine DE repeated immediately on stopping exercise. For comparison, 10 normal controls (age 41 +/-10 years) and five mechanical aortic valve patients (mean age 55 +/- 10 years) were studied. RESULTS: At rest: Ross procedure patients had similar Vmax (1.2 +/- 0.2 m/s), peak gradient (6 +/- 2 mmHg), mean gradient (4 +/- 1 mmHg) and EOAi (1.7 +/- 0.4 cm2/m2) to those of normal controls. Mechanical-valve patients had significantly higher Vmax (2.5 +/- 0.2 m/s, p <0.001), peak gradient (25 +/- 4 mmHg, p <0.001) and mean gradient (14 +/- 3 mmHg, p <0.001) than Ross patients and normal controls. At exercise: Ross procedure patients had similar Vmax (1.8 +/- 0.4 m/s versus 2.1 +/- 0.2, p = NS), peak gradient (14 +/- 6 mmHg versus 17 +/- 4, p = NS) and mean gradient (8 +/- 4 mmHg versus 10 +/- 2, p = NS) to normal controls, with no significant change in EOAi. Mechanical-valve patients had significantly higher Vmax (3.4 +/- 0.3, p <0.001), peak gradient (48 +/- 7 mmHg, p <0.001) and mean gradient (30 +/- 5 mmHg, p <0.001) than Ross patients and normal controls. CONCLUSIONS: Aortic valve replacement using the Ross procedure provides excellent hemodynamic results at rest and on exercise, with DE parameters indistinguishable from those of normal controls. This study provides further support for the use of the Ross procedure as a preferred method of aortic valve replacement in younger patients.

Adult↗

PubMed1998

Tramadol reduces the sweating, vasoconstriction, and shivering thresholds.

UNLABELLED: The analgesic tramadol inhibits the neuronal reuptake of norepinephrine and 5-hydroxytryptamine, facilitates 5-hydroxytryptamine release, and activates mu-opioid receptors. Each of these actions is likely to influence thermoregulatory control. We therefore tested the hypothesis that tramadol inhibits thermoregulatory control. Eight volunteers were evaluated on four study days, on which they received no drugs, tramadol 125 mg, tramadol 250 mg, and tramadol 250 mg with naloxone, respectively. Skin and core temperatures were gradually increased until sweating was observed and then decreased until vasoconstriction and shivering were detected. The core temperature triggering each response defined its threshold. Tramadol decreased the sweating threshold by -1.03 +/- 0.67 degrees C microgram-1.mL (r2 = 0.90 +/- 0.12). Tramadol also decreased the vasoconstriction threshold by -3.0 +/- 4.0 degrees C microgram-1.mL (r2 = 0.94 +/- 0.98) and the shivering threshold by -4.2 +/- 4.0 degrees C microgram-1.mL(r2 = 0.98 +/- 0.98). The sweating to vasoconstriction interthreshold range nearly doubled from 0.3 +/- 0.4 degree C to 0.7 +/- 0.6 degree C during the administration of large-dose tramadol (P = 0.04). The addition of naloxone only partially reversed the thermoregulatory effects of tramadol. The thermoregulatory effects of tramadol thus most resemble those of midazolam, another drug that slightly decreases the thresholds triggering all three major autonomic thermoregulatory defenses. In this respect, both drugs reduce the "setpoint" rather than produce a generalized impairment of thermoregulatory control. Nonetheless, tramadol nearly doubled the interthreshold range at a concentration near 200 ng/mL. This indicates that tramadol slightly decreases the precision of thermoregulatory control in addition to reducing the setpoint. IMPLICATIONS: The authors evaluated the effects of the analgesic tramadol on the three major thermoregulatory responses: sweating, vasoconstriction, and shivering. Tramadol had only slight thermoregulatory effects. Its use is thus unlikely to provoke hypothermia or to facilitate fever.

Adult↗

PubMed1998

Meperidine and alfentanil do not reduce the gain or maximum intensity of shivering.

BACKGROUND: Thermoregulatory shivering can be characterized by its threshold (triggering core temperature), gain (incremental intensity increase with further core temperature deviation), and maximum intensity. Meperidine (a combined mu- and kappa-agonist) treats shivering better than equianalgesic doses of pure mu-opioid agonists. Meperidine's special antishivering action is mediated, at least in part, by a disproportionate decrease in the shivering threshold. That is, meperidine decreases the shivering threshold twice as much as the vasoconstriction threshold, whereas alfentanil (a pure mu-agonist) decreases the vasoconstriction and shivering thresholds comparably. However, reductions in the gain or maximum shivering intensity might also contribute to the clinical efficacy of meperidine. Accordingly, we tested the hypothesis that meperidine reduces the gain and maximum intensity of shivering much more than alfentanil does. METHODS: Ten volunteers were each studied on three separate days: (1) control (no drug); (2) a target total plasma meperidine concentration of 1.2 microg/ml; and (3) a target plasma alfentanil concentration of 0.2 microg/ml. Skin temperatures were maintained near 31 degrees C, and core temperatures were decreased by central-venous infusion of cold lactated Ringer's solution until maximum shivering intensity was observed. Shivering was evaluated using oxygen consumption and electromyography. A sustained increase in oxygen consumption identified the shivering threshold. The gain of shivering was calculated as the slope of the oxygen consumption versus core temperature regression, and as the slope of electromyographic intensity versus core temperature regression. RESULTS: Meperidine and alfentanil administration significantly decreased the shivering thresholds. However, neither meperidine nor alfentanil reduced the gain of shivering, as determined by either oxygen consumption or electromyography. Opioid administration also failed to significantly decrease the maximum intensity of shivering. CONCLUSIONS: The authors could not confirm the hypothesis that meperidine reduces the gain or maximum intensity of shivering more than alfentanil does. These results suggest that meperidine's special antishivering effect is primarily mediated by a disproportionate reduction in the shivering threshold.

Adjuvants, Anesthesia↗