Mild therapeutic hypothermia has been shown to improve outcome for patients after cardiac arrest and may be beneficial for ischaemic stroke and myocardial ischaemia patients. However, in the awake patient, even a small decrease of core temperature provokes vigorous autonomic reactions–vasoconstriction and shivering–which both inhibit efficient core cooling. Meperidine and skin warming each linearly lower vasoconstriction and shivering thresholds. We tested whether a combination of skin warming and a medium dose of meperidine additively would reduce the shivering threshold to below 34°C without producing significant sedation or respiratory depression.
Eight healthy volunteers participated on four study days: (1) control, (2) skin warming (with forced air and warming mattress), (3) meperidine (target plasma level: 0.9 μg/ml), and (4) skin warming plus meperidine (target plasma level: 0.9 μg/ml). Volunteers were cooled with 4°C cold Ringer lactate infused over a central venous catheter (rate ≈ 2.4°C/hour core temperature drop). Shivering threshold was identified by an increase of oxygen consumption (+20% of baseline). Sedation was assessed with the Observer's Assessment of Alertness/Sedation scale.
Control shivering threshold was 35.5°C ± 0.2°C. Skin warming reduced the shivering threshold to 34.9°C ± 0.5°C (p = 0.01). Meperidine reduced the shivering threshold to 34.2°C ± 0.3°C (p < 0.01). The combination of meperidine and skin warming reduced the shivering threshold to 33.8°C ± 0.2°C (p < 0.01). There were no synergistic or antagonistic effects of meperidine and skin warming (p = 0.59). Only very mild sedation occurred on meperidine days.
A combination of meperidine and skin surface warming reduced the shivering threshold to 33.8°C ± 0.2°C via an additive interaction and produced only very mild sedation and no respiratory toxicity.
Dantrolene is used for treatment of life-threatening hyperthermia, yet its thermoregulatory effects are unknown. We tested the hypothesis that dantrolene reduces the threshold (triggering core temperature) and gain (incremental increase) of shivering. With IRB approval and informed consent, healthy volunteers were evaluated on two random days: control and dantrolene (≈2.5 mg/kg plus a continuous infusion). In study 1, 9 men were warmed until sweating was provoked and then cooled until arterio-venous shunt constriction and shivering occurred. Sweating was quantified on the chest using a ventilated capsule. Absolute right middle fingertip blood flow was quantified using venous-occlusion volume plethysmography. A sustained increase in oxygen consumption identified the shivering threshold. In study 2, 9 men were given cold Ringer's solution IV to reduce core temperature ≈2°C/h. Cooling was stopped when shivering intensity no longer increased with further core cooling. The gain of shivering was the slope of oxygen consumption vs. core temperature regression. In Study 1, sweating and vasoconstriction thresholds were similar on both days. In contrast, shivering threshold decreased 0.3±0.3°C, P=0.004, on the dantrolene day. In Study 2, dantrolene decreased the shivering threshold from 36.7±0.2 to 36.3±0.3°C, P=0.01 and systemic gain from 353±144 to 211±93 ml·min−1·°C−1, P=0.02. Thus, dantrolene substantially decreased the gain of shivering, but produced little central thermoregulatory inhibition.
Temperature: hyperthermia, fever; Pharmacology: dantrolene; Complications: shivering
Ondansetron, a serotonin-3 receptor antagonist, reduces postoperative shivering. Drugs that reduce shivering usually impair central thermoregulatory control and may thus be useful for preventing shivering during induction of therapeutic hypothermia. We determined, therefore, whether ondansetron reduces the major autonomic thermoregulatory response thresholds (trigging core temperatures) in humans.
Ten healthy volunteers were studied on two days: Control and Ondansetron (intravenous infusion to plasma concentrations of 278 (57) ng mL−1, 234 (55) ng mL−1, and 243 (58) ng mL−1at the sweating, vasoconstriction, and shivering thresholds, respectively); this corresponded to ≈50 mg of ondansetron which is roughly ten times the dose used for postoperative nausea and vomiting. Each day, skin and core temperatures were increased to provoke sweating, then reduced to elicit peripheral vasoconstriction and shivering. We determined the core-temperature sweating, vasoconstriction, and shivering thresholds after compensating for changes in mean-skin temperature. Data were analyzed with paired t tests and presented as means (SD)s; P<0.05 was statistically significant.
Ondansetron did not change the sweating (Control: 37.4 (0.4)°C, Ondansetron: 37.6 (0.3)°C, P=0.16), vasoconstriction (37.0 (0.5) vs. 37.1 (0.3)°C; P=0.70), or shivering threshold (36.3 (0.5) vs. 36.3 (0.6)°C; P=0.76). No sedation was observed on either study day.
Ondansetron, therefore, appears to have little potential for facilitating induction of therapeutic hypothermia.
Thermoregulation; ondansetron; therapeutic hypothermia
The analgesic nefopam does not compromise ventilation, is minimally sedating, and is effective as a treatment for postoperative shivering. We evaluated the effects of nefopam on the major thermoregulatory responses in humans: sweating, vasoconstriction, and shivering.
Nine volunteers were studied on three randomly assigned days: 1) control (Saline), 2) nefopam at a target plasma concentration of 35 ng/ml (Small Dose), and 3) nefopam at a target concentration of 70 ng/ml (Large Dose, ≈20 mg total). Each day, skin and core temperatures were increased to provoke sweating and then reduced to elicit peripheral vasoconstriction and shivering. We determined the thresholds (triggering core temperature at a designated skin temperature of 34°C) by mathematically compensating for changes in skin temperature using the established linear cutaneous contributions to control of each response.
Nefopam did not significantly modify the slopes for sweating (0.0 ± 4.9°C·μg−1·ml; r2 = 0.73 ± 0.32) or vasoconstriction (−3.6 ± 5.0°C·μg−1·ml; r2=−0.47± 0.41). In contrast, nefopam significantly reduced the slope of shivering (−16.8 ± 9.3°C·μg−1·ml; r2 = 0.92 ± 0.06). Large-Dose nefopam thus reduced the shivering threshold by 0.9 ± 0.4°C (P<0.001) without any discernable effect on the sweating or vasoconstriction thresholds.
Most drugs with thermoregulatory actions — including anesthetics, sedatives, and opioids — synchronously reduce the vasoconstriction and shivering thresholds. Nefopam however reduced only the shivering threshold. This pattern has not previously been reported for a centrally acting drug. That pharmacologic modulation of vasoconstriction and shivering can be separated is of clinical and physiologic interest.
Temperature; Thermoregulation; Nefopam; Shivering; Vasoconstriction; Threshold; Hypothermia
We determined the effects of doxapram on the major autonomic thermoregulatory responses in humans. Nine healthy volunteers were studied on two days: Control and Doxapram (intravenous infusion to a plasma concentration of 2.4 ±0.8 μg/mL, 2.5 ±0.9 μg/mL, and 2.6 ±1.1 μg/mL at the sweating, vasoconstriction, and shivering thresholds, respectively). Each day, skin and core temperatures were increased to provoke sweating, then reduced to elicit peripheral vasoconstriction and shivering. We determined the sweating, vasoconstriction, and shivering thresholds with compensation for changes in skin temperature. Data were analyzed with paired t tests and presented as means ± SDs; P < 0.05 was considered statistically significant. Doxapram did not change the sweating (Control: 37.5±0.4°C, Doxapram: 37.3±0.4°C, P=0.290) or the vasoconstriction threshold (36.8±0.7 vs. 36.4±0.5°C; P=0.110). However, it significantly reduced the shivering threshold from 36.2±0.5 to 35.7±0.7°C (P=0.012). No sedation or symptoms of panic were observed on either study day. The observed reduction in the shivering threshold explains the drug's efficacy for treatment of postoperative shivering; however, a reduction of only 0.5°C is unlikely to markedly facilitate induction of therapeutic hypothermia as a sole agent.
Anesthesia; Hypothermia; Temperature; Thermoregulation
Animal and human studies suggest beneficial outcome effects of mild hypothermia for stroke, for acute myocardial infarction, and for cardiogenic shock. The aim of this study was to investigate the feasibility and safety of non-invasive surface cooling for induction and maintenance of mild hypothermia (32 to 34°C) in healthy, conscious volunteers.
The trial was set at a clinical research ward in a tertiary care center, and included 16 healthy male volunteers 18 to 70 years old. Surface cooling was established by a novel non-invasive cooling pad with an esophageal target temperature of 32 to 34°C and maintenance for six hours. Shivering-control was achieved with meperidine and buspirone and additional administration of magnesium in eight subjects.
The primary endpoint to reach a target temperature of 32 to 34°C was only reached in 6 of the 16 participating subjects. Temperatures below 35°C were reached after a median cooling time of 53 minutes (38 to 102 minutes). Cooling rate was 1.1°C/h (0.7 to 1.8°C). Additional administration of magnesium had no influence on cooling rate. At no time during the cooling procedure did the participants report uncomfortable conditions for which termination of cooling had to be considered. No severe skin damage was reported.
Cooling to body temperature below 35°C by the use of non-invasive surface cooling is feasible and safe in conscious healthy volunteers. Further studies are needed to investigate an altered cooling protocol to achieve temperatures below 35°C.
human experimentation; hypothermia; magnesium; myocardial infarction; safety; stroke; temperature
Perioperative shivering is a common problem during anaesthesia. Apart from physical warming many drugs have also been used for prevention of shivering. Ketamine has been used for preventing shivering during anaesthesia in doses of 0.5 to 0.75mg kg-1, but even these doses causes too much sedation and hallucination. Ondansetron (8 mg) has been recently evaluated for its perioperative antishivering effect in patients under anaethesia. Present study was conducted to evaluate the efficacy and safety of low dose Ketamine (0.25mg kg-1) and Ondansetron (4 mg) for prevention of shivering during spinal anaesthesia.
Patients & Methods:
Total 120 patients undergoing lower abdominal surgery under spinal anaesthesia were included. 3ml of hyperbaric bupivacaine 0.5% was used for spinal anaesthesia. After intrathecal injection, the patients were randomly divided in 3 groups of 40 each who received Ketamine 0.25mg kg-1or Ondansetron 4mg IV or Saline. Vitals, temperature and shivering scores were recorded every 5 minutes. Side effects i.e. hypotension, nausea and vomiting, sedation and hallucinations were also recorded.
Fall in temperature was more significant in saline and ondansetron group (gp) than in ketamine group at all time interval. Out of 40 patients, shivering was maximum & seen in 17 patients (42.50%) in saline gp, 4 patients (10%) in ondansetron gp and in only 1patient (2.5%) in ketamine gp. Odd ratio of ketamine, ondansetron and saline are 1, 4.33 and 28.33 respectively which means that shivering in saline gp was 28.83 times higher than ketamine gp and 6.65 times higher than in ondansetron .Shivering rate was 4.33 times higher in ondansetron gp than in ketamine gp. Hypotension was lowest in ketamine gp (10%) in comparison to ondansetron gp (22.5%) and saline gp. (20%). Mild sedation was seen in almost all (95%) patients in ketamine gp,
Prophylactic low dose ketamine (0.25mg kg-1) and Ondansetron (4mg) significantly decreased shivering in patients undergoing spinal anaesthesia without significant side effects.
Shivering; Spinal anaesthesia; Ketamine; Ondansetron
Shivering associated with spinal anesthesia is uncomfortable and may interfere with monitoring. The aim of this study is to evaluate the effect of ramosetron, a serotonin-3 receptor antagonist, on the prevention of shivering during spinal anesthesia.
We enrolled 52 patients who were ASA I or II and who had undergone knee arthroscopy under spinal anesthesia. Warmed (37°) lactated Ringer's solution was infused over 15 minutes before spinal anesthesia. Patients were randomly allocated to a control group (group S, N = 26) or study group (group R, N = 26). Spinal anesthesia was performed with a 25-G Quincke-type spinal needle between the lumbar 3-4 interspace with 2.2 ml 0.5% hyperbaric bupivacaine. For patients allocated in groups S and R, 2 ml 0.9% saline and 0.3 mg ramosetron, respectively, was intravenously injected immediately before intrathecal injection at identical times. Shivering and spinal block levels were assessed immediately after the completion of subarachnoid injection, as well as 5, 10, 15, 20, 25, 30, 60, and 120 minutes after spinal anesthesia. Systolic and diastolic blood pressures, heart rate, and peripheral oxygen saturation were also recorded. Core temperatures were measured by tympanic thermometer and recorded before and during spinal anesthesia at 30-minute intervals.
Shivering was observed in 2 patients in group R and 9 patients in group S (P = 0.038, odds ratio = 6.14, 95% C.I. = 1.08-65.5). The difference in core temperature between the groups was not significant.
Compared to control, ramosetron is an effective way to prevent shivering during spinal anesthesia.
Ramosetron; Shivering; Spinal anesthesia; Thermoregulation
Heart manipulation during off-pump coronary artery bypass surgery may cause hemodynamic instability, and temporary coronary arterial occlusion may lead to myocardial ischemia. To reduce this, perioperative β-blocking agents or calcium antagonists can be administrated. The effects of perioperative administration of magnesium on myocardial function were studied in patients undergoing coronary artery bypass grafting.
The aim of the study was to evaluate the effects of preoperative magnesium administration on perioperative hemodynamia, ventricular arrhythmias and myocardial protection.
MATERIALS AND METHODS:
We reviewed 2 groups of patients undergoing off-pump coronary artery bypass surgery – 24 patients (control group) that had not received preoperative intravenous infusion of magnesium and 23 patients (treatment group) that had received preoperative intravenous magnesium sulfate.
The results demonstrated that it had reduced the heart rate, changes of ST segments, the need of β-blocking agents and the use of intra-operative intra-aortic balloon pump and the inotropic usage.
This treatment may provide hemodynamic optimization during off-pump coronary artery bypass.
Ischemia and arrhythmia; magnesium effects; off-pump coronary surgery
Cutaneous warming is reportedly an effective treatment for shivering during epidural and after general anaesthesia. We quantified the efficacy of cutaneous warming as a treatment for shivering. Unwarmed surgical patients (final intraoperative core temperatures ≈35°C) were randomly assigned to be covered with a blanket (n=9) or full-body forced-air cover (n=9). Shivering was evaluated clinically and by oxygen consumption. Forced-air heating increased mean-skin temperature (35.7±0.4 °C vs. 33.2±0.8°C, P< 0.0001) and lowered core temperature at the shivering threshold (35.7±0.2 °C vs. 36.4±0.2°C, P< 0.0001). Active warming improved thermal comfort and significantly reduced oxygen consumption from 9.7±4.4 to 5.6±1.9 mL·min−1·kg−1(P=0.038). However, duration of shivering was similar in the two groups (37±11 min [warming] and 36±10 min [control]). Core temperature thus contributed about four times as much as skin temperature to control of shivering. Cutaneous warming improved thermal comfort and reduced metabolic stress in postoperative patients, but did not quickly obliterate shivering.
shivering; body temperature; thermoregulatory control
Both caffeinol and hypothermia are neuroprotective in preclinical models of transient middle cerebral artery occlusion. We tested whether combining caffeinol and hypothermia with t-PA in acute stroke patients is safe and feasible.
20 patients with acute ischemic stroke were treated with caffeinol (caffeine 8-9 mg/kg + ethanol 0.4g/kg IV X 2 hours, started by 4 hrs after symptom onset) and hypothermia (started by 5 hrs and continued for 24 hrs (target temp 33-35°C) followed by 12 hrs of rewarming). IV t-PA was given to eligible patients. Meperidine and buspirone were used to suppress shivering.
All patients received caffeinol, and most reached target blood levels. Cooling was attempted in 18 patients via endovascular (n=8) or surface (n=10) approaches. Two patients were not cooled due to catheter or machine failure. Thirteen patients reached target temperature; average time from symptom onset was 9hrs, 43min. The last 5 hypothermia patients received surface cooling with iced saline induction and larger doses of meperidine; all patients reached target temperature, on average within 2hrs 30min from induction and 6hrs 21min from symptom onset. Three patients died: one from symptomatic hemorrhage, one from malignant cerebral edema, and one from unrelated medical complications. No adverse events were attributed to caffeinol. One patient had reduced respiratory drive due to meperidine, requiring BiPAP.
Combining caffeinol with hypothermia in acute stroke patients given IV t-PA is feasible. A prospective placebo-controlled randomized study is needed to further assess safety and to test the efficacy of caffeinol, hypothermia or both.
Therapeutic hypothermia is a means of neuroprotection well established in the management of acute ischemic brain injuries such as anoxic encephalopathy after cardiac arrest and perinatal asphyxia. As such, it is the only neuroprotective strategy for which there is robust evidence for efficacy. Although there is overwhelming evidence from animal studies that cooling also improves outcome after focal cerebral ischemia, this has not been adequately tested in patients with acute ischemic stroke. There are still some uncertainties about crucial factors relating to the delivery of hypothermia, and the resolution of these would allow improvements in the design of phase III studies in these patients and improvements in the prospects for successful translation. In this study, we discuss critical issues relating first to the targets for therapy including the optimal depth and duration of cooling, second to practical issues including the methods of cooling and the management of shivering, and finally, of factors relating to the design of clinical trials. Consideration of these factors should inform the development of strategies to establish beyond doubt the place of hypothermia in the management of acute ischemic stroke.
acute stroke; animal models; clinical trials; hypothermia; shivering MR spectroscopy
Objectives. We evaluated the efficacy of magnesium sulfate as a second-line tocolysis for 48 hours. Materials and Methods. A multi-institutional, simple 2-arm randomized controlled trial was performed. Forty-five women at 22 to 34 weeks of gestation were eligible, whose ritodrine did not sufficiently inhibit uterine contractions. After excluding 12 women, 33 were randomly assigned to either magnesium alone or combination (ritodrine and magnesium). The treatment was determined as effective if the frequency of uterine contraction was reduced by 30% at 48 hours of the treatment. Results. After magnesium sulfate infusion, 90% prolonged their pregnancy for >48 hours. Combination therapy was effective in 95% (18/19), which was significantly higher than 50% (7/14) for magnesium alone. Conclusion. This randomized trial revealed that combination therapy significantly reduced uterine contractions, suggesting that adjuvant magnesium with ritodrine is recommended, rather than changing into magnesium alone, when uterine contractions are intractable with ritodrine infusion.
Mild hypothermia is common during deep sedation or general anesthesia and is frequently associated with patient discomfort and shivering. Greater declines in temperature can produce an even greater number of significant detrimental effects. This article reviews principles of thermoregulation and influences of anesthetic agents. An understanding of these will provide a foundation for strategies to reduce heat loss and better manage patient discomfort when it occurs.
Sedation; General anesthesia; Thermoregulation; Hypothermia; Shivering
To study the effect of intravenous magnesium sulfate infusion on clinical outcome of patients of acute stroke.
Materials and Methods:
Sixty consecutive cases of acute ischemic stroke hospitalised within 24 h of an episode of stroke were taken as subjects. All subjects underwent a computed tomography head, and those found to have evidence of bleed/space-occupying lesions were excluded from the study. The subjects taken up for the study were divided into two groups of 30 subjects each. Both the groups received the standard protocol management for acute ischemic stroke. Subjects of Group 1 additionally received intravenous magnesium sulfate as initial 4 g bolus dose over 15 min followed by 16 g as slow infusion over the next 24 h. In all the subjects of the two study groups, serum magnesium levels were estimated at the time of admission (Day 0), Day 1 and Day 2 of hospitalization using an atomic absorption spectrometer.
Statistical Analysis Used:
Scandinavian stroke scores were calculated on Day 3, day of discharge and Day 28. Paired t-test was employed for comparison of stroke scores on Day 3, day of discharge and Day 28 within the same group and the unpaired t-test was used for the intergroup comparison, i.e. comparison of stroke scores of control group with corresponding stroke scores of magnesium group.
Comparison of stroke scores on Day 3 and day of discharge, on the day of discharge and Day 28 and on Day 3 and Day 28 in the magnesium group produced a t-value of 5.000 and P <0.001, which was highly significant. However, the comparison of the mean stroke scores between the magnesium and the control groups on Day 3, day of discharge and Day 28 yielded a P-value of >0.05, which was not significant.
The study failed to document a statistical significant stroke recovery in spite of achieving a significant rise in serum magnesium level, more than that necessary for neuroprotection, with an intravenous magnesium sulfate regime.
Ischemic stroke; magnesium sulfate; neuroprotection
Atrial fibrillation (AF) is the most common cardiac arrhythmia. Magnesium has been reported to be effective in reducing the incidence or prophylaxis of AF. Magnesium is also an essential constituent of many enzyme systems and plays a physiological role in coagulation regulation. The aim of the present study was to examine the effects of magnesium, whether magnesium infusion might decrease the incidence of AF and induce hypocoagulable state in patients with AF, who were undergoing mitral valve annuloplasty.
This prospective laboratory study was performed using blood from patients with AF undergoing mitral valve annuloplasty. The radial artery was punctured with a 20 gauge catheter and used for monitoring continuous arterial pressure and blood sampling. After anesthesia induction, 4 g of magnesium was mixed with 100 ml normal saline and infused for 5 minutes. Magnesium, calcium, activated clotting time (ACT) and thromboelastographic parameters were checked before and 60 minutes after the magnesium infusion. The electrocardiography changes after magnesium infusion were also checked before commencing cardiopulmonary bypass.
After magnesium infusion, the serum level of magnesium increased significantly but serum calcium did not change significantly. ACT did not change significantly before or after magnesium infusion. The thromboelastographic parameters showed no significant changes before or after magnesium infusion. None of the patients converted to sinus rhythm from AF after the magnesium infusion.
A magnesium infusion did not influence the course of AF and coagulation in patients during prebypass period with AF undergoing mitral valve annuloplasty.
Atrial fibrillation; Magnesium; Mitral valve annuloplasty; Thromboelastography
Potentiating the effect of intrathecal local anesthetics by addition of intrathecal opiods for intra-abdominal surgeries is known. In this study by addition of fentanyl we tried to minimize the dose of bupivacaine, thereby reducing the side effects caused by higher doses of intrathecal bupivacaine in cesarean section.
Study was performed on 120 cesarean section parturients divided into six groups, identified as B8, B10 and B 12.5 8.10 and 12.5 mg of bupivacaine mg and FB8, FB10 and FB 12.5 received a combination of 12.5 μg intrathecal fentanyl respectively. The parameters taken into consideration were visceral pain, hemodynamic stability, intraoperative sedation, intraoperative and postoperative shivering, and postoperative pain.
Onset of sensory block to T6 occurred faster with increasing bupivacaine doses in bupivacaine only groups and bupivacaine -fentanyl combination groups. Alone lower concentrations of bupivacaine could not complete removed the visceral pain. Blood pressure declined with the increasing concentration of Bupivacaine and Fentanyl. Incidence of nausea and shivering reduces significantly whereas, the postoperative pain relief and hemodynamics increased by adding fentanyl. Pruritis, maternal respiratory depression and changes in Apgar score of babies do not occur with fentanyl.
Spinal anesthesia among the neuraxial blocks in obstetric patients needs strict dose calculations because minimal dose changes, complications and side effects arise, providing impetus for this study. Here the synergistic, potentiating effect of fentanyl (an opiod) on bupivacaine (a local anesthetic) in spinal anesthesia for cesarian section is presented, fentanyl is able to reduce the dose of bupivacaine and therefore its harmful effects.
The marked improvement in outcome following induction of hypothermia after cardiac arrest has spurred the search for better methods to induce cooling. A regulated decrease in core temperature mediated by a drug-induced reduction in the set point for thermoregulation may be an ideal means of inducing hypothermia. To this end, the exploratory drug HBN-1 was assessed as a means to induce mild and prolonged hypothermia.
Free moving rats were infused i.v. for 12 hours with: a vehicle at room temperature (normothermia), a vehicle chilled to 4°C (forced hypothermia), or HBN-1 (mixture of ethanol, lidocaine, and vasopressin) at room temperature. Core (intra-abdominal) temperature (Tc) was measured telemetrically, tail skin temperature (Ttail) by infrared thermography, metabolic rate (MR) was estimated with indirect calorimetery, and shivering was scored visually.
HBN-1 elicited a reduction in Tc from 37.5°C to 34°C within 80 minutes after initiation of the infusion; Tc was maintained between 33°C and 34°C for more than 13 hours. HBN-1 infusion was associated with a reduction in MR (p=0.0006), a slight reduction in Ttail, and no evidence of shivering (p<0.001). The forced hypothermia group displayed shivering (p<0.001), a significant increase in MR, and a decrease in Ttail, indicative of peripheral vasoconstriction to reduce heat loss.
HBN-1 infusion induced a mild and prolonged hypothermia in free moving, unanesthetized rats characterized by modulation of thermoeffectors to reduce heat gain and increase heat loss. HBN-1 thus appears to elicit regulated hypothermia and may provide a new method for achieving a prolonged state of therapeutic hypothermia.
There has been longstanding controversy over the use of magnesium sulfate infusion in the medical management of aneurysmal subarachnoid hemorrhage (SAH). Several clinical trials evaluating the beneficial effects of magnesium on cerebral vasospasm and their poor outcome have been published. However, results from the majority of these studies have been inconclusive. This meta-analysis was performed to evaluate the effectiveness of magnesium on patient outcomes after aneurysmal SAH.
Materials and Methods:
PubMed and the Cochrane library were searched for controlled clinical trials assessing the efficacy of magnesium sulfate infusion after aneurysmal SAH. Eight studies consisting of 936 patients were included.
There was a decreased risk of poor outcome at 3–6 months after SAH in magnesium treatment groups when compared to placebo [0.78 (95% CI 0.66–0.93)]. Poor outcome was defined as severe disability, persistent vegetative state, or death, as measured by the Glasgow outcome scale (GOS), extended Glasgow outcome scale (GOSE) or modified Rankin scale (mRS). The risk of mortality after SAH was unaffected by magnesium treatment [RR 0.68 (95% CI 0.58–1.27)].
Magnesium sulfate infusion decreases risk of poor outcome after aneurysmal SAH. Current studies in the literature do not suggest a role for magnesium sulfate in mortality reduction after SAH.
Cerebral vasospasm; delayed cerebral ischemia; magnesium sulfate; subarachnoid hemorrhage
Homoiothermic organisms react to hypothermia by shivering and thermogenesis to retain their euthermic state. This reactive homeostatic mechanism recruits a strong sympathetic response, which must be suppressed by anesthesia and adjuvants during induced hypothermia. Below 30° C there is significant neural and organ depression associated with cold narcosis. Cardiac arrhythmias and ventricular fibrillation are grave developments when the core temperature is below 28° C. Proper cardiopulmonary support must be instituted in a patient who has induced or accidental hypothermia at these severely hypothermic levels.
Although clinical hypothermia is used to protect the brain and the heart from ischemic insults during an operation, it induces a complex array of physiologic changes in the body that must be appreciated so that optimal care may be provided to a patient.
The present study was designed to evaluate the efficacy of clonidine, butorphanol, and tramadol in control of shivering under spinal anesthesia, and to compare their side effects.
This randomized, prospective study was conducted in 90 patients who developed shivering under spinal anesthesia during various abdominal or orthopedic surgery procedures. On shivering, patients were randomly allocated to receive an intravenous, 1 mL bolus dose of 50 mg tramadol, or 1 mg butorphanol, or 150 μg clonidine, in a double blinded manner. Control of shivering, time taken for cessation, recurrence, hemodynamic changes, axillary temperatures, and side effects were noted and compared for all 3 groups. Collected data were analyzed using appropriate statistical tests.
Butorphanol and tramadol were more effective than clonidine in suppressing shivering. Butorphanol, tramadol, and clonidine completely controlled rigors in 83%, 73%, and 53% of cases, respectively, and incompletely suppressed rigors in 16%, 26%, and 46% of cases, respectively. Time taken to terminate rigors was significantly higher for clonidine (3.3 ± 0.9 minutes) than for butorphanol and tramadol (2.1 ± 1.0 minutes and 1.8 ± 0.5 minutes; P < 0.001).
Butorphanol had an edge over tramadol in controlling shivering with lower chances of recurrence, though both were superior to clonidine for this purpose with an early onset of action. We conclude that both these opioids control rigors better than α-2 agonists.
perioperative shivering; spinal anesthesia; tramadol; clonidine; butorphanol; thermoregulatory center
Objectives: The study compares the efficacy of two active and one passive warming interventions in healthy volunteers with induced mild hypothermia.
Methods: Eight volunteers were studied in a random order crossover design. Each volunteer was studied during re-warming from a core temperature of 35°C with each of: a radiant warmer (Fisher & Paykel); a forced air warmer (Augustine Medical), and a polyester filled blanket, to re-warm.
Results: No significant differences in re-warming rates were observed between the three warming devices. It was found that the subject's endogenous heat production was the major contributor to the re-warming of these volunteers. Metabolic rates of over 350 W were seen during the study.
Conclusions: For patients with mild hypothermia and in whom shivering is not contraindicated our data would indicate that the rate of re-warming would be little different whether a blanket or one of the two active devices were used. In the field, this may provide the caregiver a useful choice.
The protection of high magnesium on infarct size remains controversial.
To examine the effects of magnesium administered before ischemia or early in reperfusion on infarct size in a rat model of global ischemia
Isolated rat hearts were submitted to 40 min of normothermic global ischemia and 2 h of reperfusion. After 20 min of stabilization, four protocols were performed: ischemic control (IC) hearts; 15 mM of magnesium chloride administered 15 min before ischemia (MgI); 15 mM of magnesium chloride administered during the first 15 min of reperfusion (MgR); or 15 mM magnesium plus 5 mM calcium (Mg+Ca) before ischemia. Infarct size was measured by triphenyltetrazolium staining. Contractile function was assessed by left ventricular developed pressure and the maximal velocity of rise of left ventricular presssure.
The infarct size in IC hearts was 44±5%. In MgI and MgR hearts, the infarct diminished to 4.5±1.5% and 18±4%, respectively. In Mg+Ca hearts, the protection was also obtained (19±3%). Myocardial function also improved significantly by magnesium treatment. At the end of reperfusion, left ventricular developed pressure and maximal velocity of rise of left ventricular pressure values were 23±6% and 22±3% in MgI; and 10±3% and 9±2.6% in MgR versus 2±0.7% and 2.3±0.8% in IC hearts, respectively.
The treatment with magnesium either before ischemia or early in reperfusion has an infarct size limiting effect in a model of global ischemia. This protective effect is partially due to its calcium antagonistic action.
Infarct size; Ischemia; Magnesium; Reperfusion
In experimentally induced myocardial infarction, mild hypothermia (33–35°C) is beneficial if applied prior to ischemia or reperfusion. Hypothermia, when applied after reperfusion seems to confer little or no benefit. The mechanism by which hypothermia exerts its cell-protective effect during cardiac ischemia remains unclear. It has been hypothesized that hypothermia reduces the reperfusion damage; the additional damage incurred upon the myocardium during reperfusion. Reperfusion results in a massive increase in blood flow, reactive hyperemia, which may contribute to reperfusion damage. We postulated that hypothermia could attenuate the post-ischemic reactive hyperemia.
Sixteen 25–30 kg pigs, in a closed chest model, were anesthetized and temperature was established in all pigs at 37°C using an intravascular cooling catheter. The 16 pigs were then randomized to hypothermia (34°C) or control (37°C). The left main coronary artery was then catheterized with a PCI guiding catheter. A Doppler flow wire was placed in the mid part of the LAD and a PCI balloon was then positioned proximal to the Doppler wire but distal to the first diagonal branch. The LAD was then occluded for ten minutes in all pigs. Coronary blood flow was measured before, during and after ischemia/reperfusion.
The peak flow seen during post-ischemic reactive hyperemia (during the first minutes of reperfusion) was significantly reduced by 43 % (p < 0.01) in hypothermic pigs compared to controls.
Mild hypothermia significantly reduces post-ischemic hyperemia in a closed chest pig model. The reduction of reactive hyperemia during reperfusion may have an impact on cardiac reperfusion injury.
Postoperative hypothermia and shivering is a frequent event in patients during cesarean section under spinal anesthesia. We assessed the effect of preoperative warming during cesarean delivery under spinal anesthesia for prevention of hypothermia and shivering.
Forty five patients undergoing elective cesarean section were randomly assigned to three groups. Group F received warmed intravenous fluid (40℃). Group A patients were actively warmed by forced air-warming. Group C was the control group. Forced air-warming and warmed fluid was maintained for the 15 min preceding spinal anesthesia. Core temperature (tympanic membrane) and the skin temperature of arm and thigh were measured and shivering was graded simultaneously.
The core temperature at 45 min decreased less in Groups F and A than Group C (-0.5℃ ± 0.3℃ vs -0.6℃ ± 0.4℃ vs -0.9℃ ± 0.4℃, respectively; P = 0.004). The arm temperature at 15 min and 30 min exhibited a greater increase in Group A than Group F and Group C (P = 0.001 and P = 0.012, respectively). Leg temperature increased similarly among the three groups. The incidence of shivering was significantly less in Group A and Group F than Group C (20%, 13.3%, and 53.3%, respectively; P = 0.035).
Preoperative forced air-warming and warmed fluid prevents hypothermia and shivering in patients undergoing elective cesarean delivery with spinal anesthesia.
Cesarean section; Shivering; Spinal anesthesia; Warming