Intrathecal clonidine does not reduce post-spinal shivering

BACKGROUND: After general or epidural anesthesia, clonidine is known to be effective in suppressing established shivering. The aim of this study was to assess the preventive effect of intrathecal clonidine on post-spinal shivering compared with intravenous (i.v.) clonidine. METHODS: One hundred and fifty patients scheduled for orthopedic surgery were randomly allocated into three groups to receive either 1 microg/kg clonidine i.v. (IV group) or the same volume of isotonic saline (control and IT groups) at 5 min before spinal anesthesia. Spinal anesthesia was performed with 12-15 mg hyperbaric bupivacaine 0.5% plus either 1 ml of saline (control and IV groups) or 150 microg clonidine (IT group). Shivering was evaluated for a period of 90 min and graded as none, mild, moderate, and severe. RESULTS: Twenty patients (40%) in the control group and 17 patients (34%) in the IT group showed shivering compared with four (8%) in the IV group. Patients with moderate-to-severe shivering were only seen in the control and IT group, and the maximal intensity of shivering was not different between the two groups. Patients in the IV group were significantly more sedated than the other groups. CONCLUSIONS: The intrathecal administration of clonidine 150 microg fails to prevent post-spinal shivering; by contrast, we have confirmed that i.v. clonidine 1 microg/kg is an effective method to prevent shivering in patients undergoing spinal anesthesia for orthopedic surgery.     

Magnesium sulfate does not reduce postoperative analgesic requirements

BACKGROUND: Because magnesium blocks the N-methyl-D-aspartate receptor and its associated ion channels, it can prevent central sensitization caused by peripheral nociceptive stimulation. However, transport of magnesium from blood to cerebrospinal fluid (CSF) across the blood-brain barrier is limited in normal humans. The current study was designed to evaluate whether perioperative intravenous magnesium sulfate infusion affects postoperative pain. METHODS: Sixty patients undergoing abdominal hysterectomy received 50 mg/kg intravenous magnesium sulfate as a bolus dose followed by a continuous infusion of 15 mg x kg(-1) x h(-1) for 6 h (magnesium group) or the same volume of isotonic saline (control group). At the end of surgery, serum and CSF magnesium concentration were measured in both groups. The cumulative postoperative analgesic consumption was measured to assess the analgesic effect using a patient-controlled epidural analgesia device. Pain intensities at rest and during forced expiration were evaluated at 6, 24, 48, and 72 h postoperatively. RESULTS: At the end of surgery, patients in the magnesium group had significantly greater postoperative serum magnesium concentrations compared with both preoperative and control group values (P < 0.001). Despite significantly higher serum magnesium concentrations in the magnesium group, there was no significant difference in magnesium concentration measured in postoperative CSF. Cumulative postoperative analgesic doses were similar in both groups. However, there was observed an inverse relation between cumulative postoperative analgesic consumption and the CSF magnesium concentration in both groups. Visual analog pain scores at rest and during forced expiration were similar and less than 4 in both groups. CONCLUSIONS: Perioperative intravenous administration of magnesium sulfate did not increase CSF magnesium concentration and had no effects on postoperative pain. However, an inverse relation between cumulative postoperative analgesic consumption and the CSF magnesium concentration was observed. These results suggest that perioperative intravenous magnesium infusion may not be useful for preventing postoperative pain.     

Chitosan does not reduce post-prandial urinary oxalate excretion

Chitosan is a positively charged non-absorbable cellulose-like fibrillar biopolymer derived from shellfish which forms films with negatively charged surfaces. We hypothesized that negatively charged oxalate in the intestinal lumen could attach to the positively charged tertiary amino group of chitosan. We studied the effects of chitosan on intestinal oxalate absorption by measuring urinary oxalate excretion following an oral oxalate load with and without accompanying oral chitosan. The subjects consumed a fixed diet and collected urine for 24 h, in divided periods, during control and experimental protocols. Urine was collected with HCl and thymol as a preservative. For the control period, the subjects consumed an oxalate load, 50 g of cooked spinach, with water for lunch; the post-prandial urine collection was divided into three periods of 2 h. For the experimental period, 1 week later, the subjects consumed the same diet as that during the control period, but added 2 g of chitosan to the oxalate load. Post-prandial urinary oxalate excretion was expressed as mg oxalate/g creatinine. The spinach load was associated with a significant post-prandial increase in urinary oxalate during the control period of 25.7±12.8 mg/g creatinine. Accompanying the oxalate load with chitosan was well tolerated. There was no decrease in post-prandial urinary oxalate excretion during the experimental period: oxalate excretion rose by 31.3±16.9 mg/g creatinine (P=0.57, NS). We conclude that chitosan does not reduce acute intestinal oxalate absorption and therefore does not affect post-prandial urinary oxalate excretion.     

Adjunctive analgesia with intravenous propacetamol does not reduce morphine-related adverse effects

Background. Propacetamol is widely used in the management ofpostoperative pain. It decreases morphine requirements but itseffect on the incidence of morphine-related adverse effectsremains unknown. Methods. Patients (550) were randomly assigned to receive propacetamolor a placebo over the first 24 h after operation in a blindedstudy. Intravenous morphine titration was performed, after whichmorphine was administered s.c. every 4 h according to theirpain score. Pain was assessed using a visual analogue scale(VAS). The primary end-point was the incidence of morphine-relatedadverse effects. The main secondary end-points were morphinerequirements and VAS score. Results. After morphine titration, the VAS score and the numberof patients with pain relief did not differ between groups.Morphine requirements were decreased in the propacetamol group(21 vs 14.5 mg, P<0.001) but the incidence of morphine-relatedadverse effects did not differ between groups (42 vs 46%, notsignificant). In patients with moderate pain (n=395), morphinerequirements decreased by 37% (P<0.001) and the percentageof patients requiring no morphine was greater (21 vs 8%, P=0.002)in the propacetamol group. In patients with severe pain (n=155),morphine requirements decreased by 18% (P=0.04) in the propacetamolgroup and the number of patients who did not require morphine(3 vs 8%) did not differ significantly. Conclusions. Although propacetamol induced a small morphine-sparingeffect, it did not change the incidence of morphine-relatedadverse effects in the postoperative period. Moreover, no benefitcould be demonstrated in patients with severe postoperativepain. Br J Anaesth 2003; 90: 314–19     

General anesthesia does not reduce life expectancy in aged rats

A recent clinical study demonstrated that deep anesthesia, as measured by Bispectral index monitoring, was associated with increased 1-yr mortality among middle-aged and elderly surgical patients. We have previously demonstrated impaired cognitive performance in aged rats for weeks after general anesthesia with 1.2% isoflurane-70% nitrous oxide-30% oxygen. However, the effects of 2 h of anesthesia with 1.2% isoflurane-70% nitrous oxide-30% oxygen on rodent life expectancy are unknown and may have confounded our results. Accordingly, we designed this study to determine if general anesthesia alters life expectancy in aged rats. Sixteen 22-mo-old Fischer 344 rats were randomized to anesthesia for 2 h with 1.2% isoflurane-70% nitrous oxide-30% oxygen or a control group that received 30% oxygen (n = 8 per group). Rats recovered in an enriched oxygen environment and then were placed in their home cage under routine conditions. The number of days between anesthesia administration and death were recorded and Kaplan-Meier survival curves generated and compared statistically using the log-rank test and bootstrap method. There was no difference in long-term survival between the control and anesthesia groups. Hence, general anesthesia with 1.2% isoflurane-70% nitrous oxide-30% oxygen does not reduce life expectancy in aged Fischer 344 rats.     

Ondansetron does not reduce the shivering threshold in healthy volunteers

Background. Ondansetron, a serotonin-3 receptor antagonist,reduces postoperative shivering. Drugs that reduce shiveringusually impair central thermoregulatory control, and may thusbe useful for preventing shivering during induction of therapeutichypothermia. We determined, therefore, whether ondansetron reducesthe major autonomic thermoregulatory response thresholds (triggeringcore temperatures) in humans. Methods. Control (placebo) and ondansetron infusions at thetarget plasma concentration of 250 ng ml^–1 were studiedin healthy volunteers on two different days. Each day, skinand core temperatures were increased to provoke sweating; thenreduced to elicit peripheral vasoconstriction and shivering.We determined the core-temperature sweating, vasoconstrictionand shivering thresholds after compensating for changes in mean-skintemperature. Data were analysed using t-tests and presentedas means (SDs); P<0.05 was taken as significant. Results. Ondensetron plasma concentrations were 278 (57), 234(55) and 243 (58) ng ml^–1 at the sweating, vasoconstrictionand shivering thresholds, respectively; these corresponded to50 mg of ondansetron which is approximately 10 times the doseused for postoperative nausea and vomiting. Ondansetron didnot change the sweating (control 37.4 (0.4)°C, ondansetron37.6 (0.3)°C, P=0.16), vasoconstriction (37.0 (0.5)°Cvs 37.1 (0.3)°C; P=0.70), or shivering threshold (36.3 (0.5)°Cvs 36.3 (0.6)°C; P=0.76). No sedation was observed on eitherstudy day. Conclusions. Ondansetron appears to have little potential forfacilitating induction of therapeutic hypothermia.     

Diathermy does not reduce subconjunctival haemorrhage during sub-Tenon's block

Editor—The frequency of subconjunctival haemorrhage duringposterior sub-Tenon's block is 7–56%.^{1 2} This is usuallyconfined to the area of dissection but can spread to other quadrants.²The incidence is even higher with the use of an anterior sub-Tenon'scannula.³ The damage to fine vessels inevitably severed duringconjunctival dissection is the     

A 5-microm filter does not reduce propofol-induced pain

We assessed the effectiveness of a 5-microm filter in reducing propofol-induced pain and determined whether any reduction is due to removal of contaminants or an alteration in flow characteristics. A total of 120 unpremedicated women (ASA 1-3, aged 18-70 yr) were randomly allocated to one of three equal-sized groups. In group A, propofol was drawn up and injected through an unfiltered plastic cannula. In group B, propofol was drawn up through a 5-microm filter needle and injected through an unfiltered plastic cannula. In group C, propofol was drawn up and injected through a 5-microm filter needle. Unmodified propofol from a 20-ml rubber topped vial at room temperature was used. A 22-g cannula was inserted into the largest visible vein on the dorsum of the non-dominant hand. Propofol was administered at 0.5 ml.s-1 and patients were asked about pain every 10 s until unresponsive, by a blinded observer. The pain score for the patient was the taken as the most severe pain documented. The frequency and severity of pain were similar among groups. We conclude that a 5-microm filter does not reduce pain associated with injection of propofol drawn from a vial with a rubber bung.     

Sevoflurane anaesthesia in children after induction of anaesthesia with midazolam and thiopental does not cause epileptiform EEG

Background. Sevoflurane is a methyl ether anaesthetic commonlyused for induction and maintenance of general anaesthesia inchildren. Sevoflurane is a non-irritant and acts quickly soinduction is usually calm. However, inhalation induction withhigh concentrations of sevoflurane can cause convulsion-likemovements and seizure-like changes in the electroencephalogram(EEG). Little is known about the EEG during maintenance of anaesthesiawith sevoflurane, so we planned a prospective trial of sevofluranemaintenance after i.v. induction with benzodiazepine and barbiturate,which is another common induction technique in children. Methods. EEG recordings were made before premedication withmidazolam (0.1 mg kg^–1 i.v.), during induction ofanaesthesia with thiopental (5 mg kg^–1), and duringmaintenance with sevoflurane (2% end-tidal concentration inair/oxygen without nitrous oxide) in 30 generally healthy, 3-to 8-year-old children having adenoids removed. Noise-free EEGdata of good quality were successfully recorded from all 30children. Results. Two independent neurophysiologists did not detect epileptiformdischarges in any of the recordings. Conclusion. Premedication with midazolam, i.v. induction withthiopental and maintenance of anaesthesia with 2% sevofluranein air does not cause epileptiform EEG patterns in children. Br J Anaesth 2002; 89: 853–6     

Preoperative diclofenac does not reduce pain of laparoscopic cholecystectomy

OBJECTIVE: To study the safety and efficacy of diclofenac for preemptive analgesia in the first 24 hours after elective laparoscopic cholecystectomy (ELC). PATIENTS AND METHODS: This prospective, randomized, placebo-controlled, double-blind study enrolled 90 patients of both sexes undergoing ECL. The patients were 17 to 76 years old and weighed between 45 and 100 Kg (ASA I and II). Assignment was to one of the following groups. A control group received diclofenac before and after surgery (DD) as follows: diclofenac 1 mg/Kg i.m. 60 minutes before surgery and a loading dose of 0.35 mg/Kg i.v. after surgery followed by continuous infusion of 1.5 mg/Kg over 24 hours. The study group received diclofenac and placebo (DP) as follows: diclofenac 1 mg/Kg i.m. 60 minutes before surgery and infused saline solution after extubation. A second control group received placebo before surgery and diclofenac afterwards (PD) as follows: a physiological solution was given intramuscularly 60 minutes before the operation and diclofenac was given after extubation as in the DD group. Pain intensity was assessed on a visual analog scale at four times: 1 hour (T1), 6 hours (T2), 12 hours (T3) and 24 hours (T4) after extubation. At those times we also recorded the need for rescue analgesia and side effects. Arterial blood gases and vital signs were recorded 1 hour before surgery (T0) and at T4. RESULTS: Pain intensity at T1 was 2.67 +/- 0.54, 2.82 +/- 0.63 and 2.88 +/- 0.58 for the DD, DP and PD groups, respectively (p = 0.96). The differences in mean pain between T1 and T2, T3 and T4 were -0.2 +/- 0.66, -0.7 +/- 0.51 and 0.0 +/- 0.72 in the DD group (p = 0.723); -0.9 +/- 0.60, -0.4 +/- 0.57 and -1.3 +/- 0.65 in the DP group (p = 0.578); and -1.0 +/- 0.59, -0.5 +/- 0.77 and -1.0 +/- 0.69 in the PD group (p = 0.816). No significant differences in pain intensity or need for rescue analgesia were observed. Although 22 side effects were observed in group DD, 21 in DP and 21 in PD, none was serious. CONCLUSIONS: Simple preemptive analgesia with 1 mg/Kg i.m. of diclofenac 60 minutes before induction of anesthesia does not decrease pain intensity or the need for rescue analgesia in the first 24 hours after ELC.     

Xenon does not reduce opioid requirement for orthopedic surgery

PURPOSE: Is to test the hypothesis that 70% xenon has a relevant opioid sparing effect compared to a minimum alveolar concentration (MAC)-equivalent combination of N(2)O and desflurane. METHODS: In this randomized, controlled study of 30 patients undergoing major orthopedic surgery, we determined the plasma alfentanil concentration required to suppress response to skin incision in 50% of patients (Cp(50)) anesthetized with xenon (70%) or a combination of N(2)O (70%) and desflurane (2%). A response was defined as movement, pressor response > 15 mmHg, heart rate > 90 beats x min(-1), autonomic reactions or a combination of these. At skin incision, alfentanil was administered at a randomly selected target plasma concentration thereafter the concentration was increased or decreased according to the patient's response. After skin incision, desflurane was adjusted to maintain the bispectral index below 60 and prevent responsiveness in both groups. RESULTS: The Cp(50) (+/- standard error) of alfentanil was 83 +/- 48ng x mL(-1) with xenon and 49 +/- 26 ng x mL(-1) with N(2)O/desflurane (P =0.451). During surgery five xenon and 15 N(2)O/desflurane patients were given desflurane at 1.0 +/- 0.5 volume % and 2.5 +/- 0.7 volume %. The total age adjusted MAC was 0.97 +/- 0.07 and 0.94 +/- 0.07 respectively (P = 0.217). The intraoperative plasma alfentanil concentrations were 95 +/- 80 and 93 +/- 60 ng x mL(-1) respectively (mean +/- SD; P = 0.451). Patients given xenon were slightly more bradycardic, whereas blood pressure was similar. CONCLUSION: Xenon compared to a MAC-equivalent combination of N(2)O and desflurane does not substantially reduce opioid requirement for orthopedic surgery. A small but clinically irrelevant difference cannot be excluded, however.     

Midazolam does not reduce emergence delirium after sevoflurane anesthesia in children

Background: Behavioral disturbance in children following sevoflurane anesthesia is a relatively frequent event. The aim of this study was to evaluate whether a higher dose of preoperatively administered rectal midazolam compared with a lower would alleviate this phenomenon. Furthermore the impact of these two doses of midazolam on sedation at induction of anesthesia was compared. Methods: A total of 115 children presenting for minor surgery under anesthesia were included in the study. The children were randomized to receive rectally either 1 mg·kg⁻¹ midazolam (group H) or 0.5 mg·kg⁻¹ midazolam (group L). General anesthesia was induced with propofol or sevoflurane and maintained with 1.5% sevoflurane in the inspiratory limb. Prior to the start of surgery a regional block was performed to ensure adequate pain relief. Behavior on emergence was assessed using a three point scale. In case of severe agitation propofol was administered IV. Results: The children in group H were significantly better sedated preoperatively (P < 0.01). There was no significant difference in emergence behavior: 42.1% of children in group H compared with 36.2% of children in group L exhibited severe agitation requiring sedation with propofol (P = 0.37). However, regardless of the preoperative dose of midazolam more children under the age of 36 months (61.4%) were severely distressed at emergence compared with older children (16.7%) (P < 0.01). Conclusions: A higher dose of 1 mg·kg⁻¹ rectal midazolam results in much better sedated children on induction of anesthesia than 0.5 mg·kg⁻¹. This, however, does not result in a reduced incidence of emergence delirium after sevoflurane anesthesia. Regardless of the premedication negative behavioral changes occur more frequently in children younger than 3 years of age.     

Nicotine does not reduce blood flow to healthy bone in rats

Given the increased incidence of orthopedic complications among smokers, we tested the null hypothesis that nicotine, the most vasoactive substance in cigarettes, does not reduce blood flow to long bones. Nicotine was administered to adult rats at a rate of 2.4 or 3.6 mg/kg/d for 2 weeks to determine if nicotine has a dose-dependent effect on bone blood flow. Control rats received nicotine-free solution. After 2 weeks, the rats were anesthetized. The microsphere technique was used to measure flow to femurs and tibias. Blood was collected to measure plasma nicotine. The lower dose established a plasma level of 14 ng/mL (SEM, 4 ng/mL); the higher dose elevated nicotine to 43 ng/mL (SEM, 11 ng/mL). Neither dose altered blood flow to tibias or femurs. A higher dose or longer treatment may be required to reduce bone blood flow. Alternatively, nicotine may not reduce blood flow to healthy bone at any dose but may delay bone healing by other mechanisms (ie, inhibiting angiogenesis and/or osteogenesis).     

Deliberate arterial hypotension does not reduce intraocular pressure in pigs.

Among the accepted advantages of general anesthesia in ophthalmic surgery is improved control of intraocular pressure (IOP). Although standard textbooks advocate deliberate arterial hypotension to facilitate intraocular surgery by reducing IOP, scientific proof of such an effect is lacking. The authors investigated effects of induced arterial hypotension on IOP in an anesthetized porcine model. Forty-two piglets were anesthetized with piritramide, were placed in the prone position, and had the anterior chamber of one eye punctured with a small Teflon cannula to measure IOP. Six pigs were used in a pilot study to establish dose-response relationships for the hypotensive agents; 36 pigs were randomly allocated to one of three groups (n = 12) to receive nitroprusside, adenosine, or isoflurane to reduce mean arterial pressure (MAP) by 50%. Measurements were made after initial stabilization of hemodynamic variables and IOP (control), when a stable MAP of 0.5x control was maintained for 10 min or longer, and after return of MAP to a posthypotensive steady state. The median of differences between time intervals was analyzed statistically for all variables. Nitroprusside and adenosine produced hyperdynamic hypotension (cardiac index increased); isoflurane-induced hypotension was hypodynamic. Control IOPs were 12.9, 12.5, and 11.1 mmHg in the nitroprusside, adenosine, and isoflurane groups, respectively. Median change in IOP during hypotension was -1.5, +1.5, and 0 mmHg in the nitroprusside, adenosine, and isoflurane groups, respectively. The IOP during adenosine-induced hypotension was significantly higher than that during either nitroprusside- or isoflurane-induced hypotension. Return of MAP to control levels was frequently associated with intraocular rebound hypertension when arterial hypotension had been induced with adenosine or nitroprusside.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dexmedetomidine does not modify the neuromuscular blocking action of vecuronium in the anaesthetized rat

Dexmedetomidine is a new alpha adrenergic agonist anaestheticadjuvant. In animal studies, dexmedetomidine produced muscleflaccidity and prevented opioid-induced muscle rigidity, apparently via a central mechanism. The effect of dexmedetomidineon the neuromuscular junction or on non-depolarizing neuromuscularblock during anaesthesia has not been reported. We have studiedin the anaesthesized rat, the effects of dexmedetomidine onvecuronium-induced twitch depression. Wistar rats (n = 35) wereanaesthetized and their lungs ventilated to maintain normocapnia.An infusion of vecuronium of 2.3 (SEM 0.1) µg kg min^–1produced a stable twitch height (T1) depression of the tibialnerve of 53 (2)% of control in all groups. Rats were allocatedrandomly to receive either saline or dexmedetomidine 10, 30or 1 00 µg kg^–1 i.v. and T1 height was measuredcontinuously for 60 min. Dexmedetomidine did not significantlyaffect T1 height during the first 30 min of infusion. At latertimes there were minor differences between groups. With cessationof the infusion of vecu ronium, T1 height recovered rapidlyto normal in all groups. These data suggest that the neuromuscularblocking properties of dexmedetomidine are unlikely to be producedby action at the neuromuscular junction.      

Multimodal analgesia before thoracic surgery does not reduce postoperative paint

Several reports have suggested that preoperative nociceptiveblock may reduce postoperative pain, analgesic requirements,or both, beyond the anticipated duration of action of the analgesicagents. We have investigated, in a double-blind, placebo-controlledstudy, pre-emptive analgesia and the respiratory effects ofpreoperative administration of a multimodal antinociceptiveregimen. Thirty patients undergoing thoracotomy were allocatedrandomly to two groups. Before surgery, the treatment group(n = 15) received morphine 0.15 mg kg^–1 i.m. with perphenazine0.03mg kg^–1 i.m. and a rectal suppository of indomethacin100 mg, while the placebo group (n = 15) received midazolam0.05mg kg^–1 i.m. and a placebo rectal suppository. Afterinduction of anaesthesia, the treatment group received intercostalnerve block with 0.5% bupivacaine and adrenaline 1:200000 (3ml) in the interspace of the incision and in the two spacesabove and two spaces below. The placebo group received identicalinjections but with normal saline only. The treatment groupconsumed significantly less morphine by patient-controlled analgesiain the first 6 h after operation, but the total dose of morphineconsumed on days 2 and 3 after surgery was significantly greaterin the treatment group. There were no differences between thegroups in postoperative VAS scores (at rest or after movement),Pa_co2 values or postoperative spirometry. However, pain thresholdsto pressure applied at the side of the chest contralateral tothe site of incision decreased significantly from preoperativevalues on days 1 and 2 after surgery in both groups. The resultsof this study do not support the preoperative use of this combinedregimen for post-thoracotomy pain.      

Addition of papaverine to cardioplegia does not reduce myocardial necrosis

In a randomized, double-blind prospective study involving 495 patients, we investigated whether the addition of papaverine, 60 mg, to our existing regimen of cold cardioplegia would reduce myocardial necrosis during elective coronary artery bypass operations. Twenty-one (4.2%) patients sustained acute postoperative myocardial infarctions (MI), and 7 (1.4%) died during hospitalization. Neither MI nor death was related to papaverine supplementation. Among 469 patients without postoperative MI, levels of the myocardial-specific isoenzyme of creatine phosphokinase measured 10 hours after aortic cross-clamping were related to ischemic cross-clamp time, but not to papaverine supplementation of cardioplegia. At declamping after completion of distal anastomoses, ventricular fibrillation was more common after cardioplegia without papaverine (32% versus 9%). No other differences between the two groups were found in intraoperative and postoperative hemodynamics, difficulty of weaning from bypass, or postoperative volume requirements. We identified three risk factors for postoperative MI: ECG evidence of new ischemia prior to bypass, unusual technical difficulty with distal anastomoses for the surgeon, and prolonged time of ischemia. We conclude that addition of papaverine to our cardioplegia regimen did not affect outcome or nonspecific myocardial necrosis.