Isoflurane Alters Shivering Patterns and Reduces Maximum Shivering Intensity

Background: Shivering can be characterized by its threshold (triggering core temperature), gain (incremental intensity increase with further core hypothermia), and maximum response intensity. Isoflurane produces a clonic muscular activity that is not a component of normal shivering. To the extent that clonic activity is superimposed on normal thermoregulatory shivering, the gain of shivering might be increased during isoflurane anesthesia. Conversely, volatile anesthetics decrease systemic oxygen consumption and peripherally inhibit skeletal muscle strength, which might limit maximum intensity despite central activation. The purpose of the present study was, therefore, to evaluate the effect of isoflurane shivering patterns and the gain and maximum intensity of shivering.

Methods: Ten volunteers were each studied in two separate protocols: (1) control (no drug) and (2) 0.7% end-tidal isoflurane. On each day, the mean skin temperature was maintained at 31 [degree sign] Celsius. Core temperature was then reduced by infusion of cold fluid until shivering intensity no longer increased. The core temperature triggering the initial increase in oxygen consumption defined the shivering threshold. The gain of shivering was defined by the slope of the core temperature versus oxygen consumption regression. Pectoralis and quadriceps electromyography was used to evaluate anesthetic-induced facilitation of clonic (5-7 Hz) muscular activity.

Results: Isoflurane significantly decreased the shivering threshold from 36.4 +/- 0.3 to 34.2 +/- 0.8 [degree sign] Celsius. The increase in oxygen consumption was linear on the control day and was followed by sustained high-intensity activity. During isoflurane administration, shivering was characterized by bursts of intense shivering separated by quiescent periods. Isoflurane significantly increased the gain of shivering (as calculated from the initial increase), from -684 +/- 266 to -1483 +/- 752 ml [center dot] min sup -1 [center dot] [degree sign] Celsius sup -1. However, isoflurane significantly decreased the maximum intensity of shivering, from 706 +/- 144 to 489 +/- 80 ml/min. Relative electromyographic power in frequencies associated with clonus increased significantly when the volunteers were given isoflurane.     

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 micro- and kappa-agonist) treats shivering better than equianalgesic doses of pure micro-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 micro-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 micro gram/ml; and (3) a target plasma alfentanil concentration of 0.2 micro gram/ml. Skin temperatures were maintained near 31 [degree sign] Celsius, 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.     

Propofol Linearly Reduces the Vasoconstriction and Shivering Thresholds

Background: Skin temperature is best kept constant when determining response thresholds because both skin and core temperatures contribute to thermoregulatory control. In practice, however, it is difficult to evaluate both warm and cold thresholds while maintaining constant cutaneous temperature. A recent study shows that vasoconstriction and shivering thresholds are a linear function of skin and core temperatures, with skin contributing 20 plus/minus 6% and 19 plus/minus 8%, respectively. (Skin temperature has long been known to contribute [nearly equal] 10% to the control of sweating.) Using these relations, we were able to experimentally manipulate both skin and core temperatures, subsequently compensate for the changes in skin temperature, and finally report the results in terms of calculated core- temperature thresholds at a single designated skin temperature.

Methods: Five volunteers were each studied on 4 days: (1) control; (2) a target blood propofol concentration of 2 micro gram/ml; (3) a target concentration of 4 micro gram/ml; and (4) a target concentration of 8 micro gram/ml. On each day, we increased skin and core temperatures sufficiently to provoke sweating. Skin and core temperatures were subsequently reduced to elicit peripheral vasoconstriction and shivering. We mathematically compensated for changes in skin temperature by using the established linear cutaneous contributions to the control of sweating (10%) and to vasoconstriction and shivering (20%). From these calculated core-temperature thresholds (at a designated skin temperature of 35.7 degrees Celsius), the propofol concentration- response curves for the sweating, vasoconstriction, and shivering thresholds were analyzed using linear regression. We validated this new method by comparing the concentration-dependent effects of propofol with those obtained previously with an established model.

Results: The concentration-response slopes for sweating and vasoconstriction were virtually identical to those reported previously. Propofol significantly decreased the core temperature triggering vasoconstriction (slope = 0.6 plus/minus 0.1 degree Celsius *symbol* micro gram sup -1 *symbol* ml sup -1; r2 = 0.98 plus/minus 0.02) and shivering (slope = 0.7 plus/minus 0.1 degree Celsius *symbol* micro gram sup -1 *symbol* ml sup -1; r2 = 0.95 plus/minus 0.05). In contrast, increasing the blood propofol concentration increased the sweating threshold only slightly (slope = 0.1 plus/minus 0.1 degree Celsius *symbol* micro gram sup -1 *symbol* ml sup -1; r2 = 0.46 plus/minus 0.39).     

静注加肌注曲马多防治硬膜外麻醉期间寒战反应的研究

目的　观察曲马多防治硬膜外麻醉期间寒战反应时两种用药方法的临床效果。　方法硬膜外麻醉手术期间发生寒战的 6 0例成年患者 ,当出现寒战分级达 2～ 3级时 ,用室温下盐酸曲马多 1mg kg加氟哌啶 2 .5mg缓慢静脉推注 ,随机分成二组 :研究组 (R组 )与对照组 (C组 ) ,每组各 30例 ;R组在 5min内用上述同样药物和剂量予以肌内注射 ,C组以生理盐水 2ml肌内注射。观察寒战的治疗效果及 6h内寒战复发率。　结果　两组均于静注曲马多后 3min内起效 ,所有病人寒战反应均得到缓解 ,6h内R组均无寒战反应复发 ,C组有 5例再次出现寒战达 2级以上 ,给予追加首次量的 1 2后缓解 ,两组间差异有显著性 (P <0 .0 5 )。　结论　静注加肌注曲马多和氟哌啶可更有效地防治硬膜外麻醉期间的寒战反应。     

Hypotensive Epidural Anesthesia Reduces Blood Loss in Pelvic and Sacral Bone Tumor Resections

Background

Resection of pelvic and sacral tumors can cause severe blood loss, complications, and even postoperative death. Hypotensive epidural anesthesia has been used to mitigate blood loss after elective arthroplasty, but to our knowledge, it has not been studied as an approach that might make resection of pelvic and sacral tumors safer.

Questions/purposes

The purposes of this study were (1) to compare the blood loss and blood product use for patients undergoing pelvic and sacral tumor surgery under standard anesthesia or hypotensive epidural anesthesia; (2) to assess the frequency of end-organ damage with the two techniques; and (3) to compare 90-day mortality between the two techniques.

Methods

Between 2000 and 2014, 285 major pelvic and sacral resections were performed at one center. A total of 174 (61%) had complete data sets for analysis of blood loss, transfusion use, complications, and mortality at 90 days. Of those, 102 (59%) underwent hypotensive epidural anesthesia, whereas the remainder received standard anesthetic care. The anesthetic approach was determined by the anesthetists in charge of the case with hypotensive epidural anesthesia exclusively performed by one of two subspecialty trained anesthetists as their routine for major pelvic or sacral surgery. The groups were comparable in terms of potential confounding variables such as age, gender, tumor volume, and operation performed. Hypotensive epidural anesthesia was defined as a technique using an extensive epidural block up to T2-3 dermatome, peripherally administered low-concentration intravenous adrenaline infusion, and using unimpeded spontaneous respiration to achieve controlled hypotension, precise rate control of the heart, and enhanced velocity of venous return, all aggregated thus to minimize blood loss during pelvic surgery while preserving vital perfusion. The groups were assessed for perioperative blood loss calculated from pre- and postsurgery hemoglobin and transfusion use as well as postoperative complications, morbidity, and mortality at 90 days.

Results

There was less mean blood loss in the hypotensive epidural anesthesia group (1457 mL, SD 1721, 95% confidence interval [CI], 1114–1801 versus 2421 mL, SD 2297, 95% CI, 1877–2965; p = 0.003). Patients in the hypotensive epidural anesthesia group on average received fewer packed red cell transfusions (2.7 units, SD 2.9, 95% CI, 2.1–3.2 versus 3.9 units, SD 4.4, 95% CI, 2.9–5.0; p = 0.03). There were no differences in the proportions of patients experiencing end-organ injury (7%, n = seven of 102 versus 6%, n = four of 72; p = 0.72). With the numbers available, there was no difference in 90-day mortality rate between groups (1.9%, n = two of 102 versus 1.3%, n = one of 72; p = 0.77).

Conclusions

We found that hypotensive epidural anesthesia resulted in less blood loss, fewer transfusions, and no apparent increase in serious complications in pelvic and sacral tumor surgery performed in the setting of a high-volume tertiary sarcoma referral hospital. We recommend that further collaborative studies be undertaken to confirm our results with hypotensive epidural anesthesia in surgery for pelvic tumors.

Level of Evidence

Level III, therapeutic study.

     

The Local Addition of Tenoxicam Reduces the Incidence of Low Back Pain after Lumbar Epidural Anesthesia

Background: Postepidural backache is a common postoperative complaint after lumbar epidural anesthesia. Useful interventions to decrease the incidence of postepidural backache would be helpful.

Methods: We performed a prospective, randomized, double-blind study to compare the effect of local addition of tenoxicam on the incidence of postepidural backache after nonobstetric surgery. One thousand unpremedicated ASA physical status I or II patients scheduled for hemorrhoidectomy were assigned randomly to tenoxicam or control groups. Patients in the control group received 25 ml lidocaine, 2%, with epinephrine 1:200,000 epidurally and 4 ml lidocaine, 1%, for local skin infiltration. Patients in the tenoxicam group received 25 ml lidocaine, 2%, with epinephrine 1:200,000 epidurally and 4 ml lidocaine, 1%, with tenoxicam (2 mg) 1:2,000 for local skin infiltration. Patients were interviewed at 24, 48, and 72 h postoperatively using a standard visual analog scale for evaluation of postepidural backache. A patient was considered to have postepidural backache when the postoperative visual analog scale score was higher than the preoperative score.

Results: The incidence of postepidural backache in patients in the control group for the 3 days were 22.8%, 17.4%, and 9.2%, all of which were significantly more frequent than observed in the patients in the tenoxicam group (6.8%, 4.0%, and 1.2%, P < 0.01). There was a significant association between backache and multiple attempts at epidural needle insertion.     

Epidural Anesthesia Retards Intestinal Acidosis and Reduces Portal Vein Endotoxin Concentrations during Progressive Hypoxia in Rabbits

Background: Because it is postulated that gut is important via bacterial translocation in the development of the systemic inflammatory response and multiple organ dysfunction, the preservation of gut integrity is a therapeutic goal for physicians who care for critically ill patients. The aim of the current study was to evaluate whether epidural anesthesia prevented gut injury and subsequent translocation of endotoxin during acute progressive hypoxia in rabbits.

Methods: After the placement of an epidural catheter, 18 male rabbits, anesthetized with buprenorphine-midazolam, were allocated randomly to two groups: 0.5% lidocaine (group E) and saline (group C) groups. The solutions (0.4 ml/kg) were injected epidurally, followed by continuous infusion (0.1 ml[middle dot]kg-1[middle dot]h-1) during the study period. Portal blood flow, portal endotoxin concentrations, and intramucosal pH (pHi) of the ileum were measured at baseline and during two stages of progressive hypoxia (fraction of inspired oxygen [Fio2] = 0.15 and 0.10).

Results: In both study groups, the portal blood flow was preserved to a similar extent during acute hypoxia. However, pHi was reduced to a lesser extent in group E (7.33 +/- 0.12 versus 7.22 +/- 0.12 at an Fio2 of 0.15 and 7.13 +/- 0.15 versus 7.03 +/- 0.12 at an Fio2 of 0.10; mean +/- SD, P < 0.01), concurrently with lower portal endotoxin concentrations (P < 0.05) compared with group C.     

哌氟合剂及红外线热幅射应用于防治硬膜外麻醉中寒战

随机选择硬膜外麻醉择期手术病人160例,分为三组,即治疗组、药物预防组和药物加红外线热幅射预防组。分别应用哌氟合剂(哌替啶25～50mg及氟哌啶2.5～5mg)及哌氟合剂加红外线热幅射防治硬膜外麻醉中寒战反应。结果表明哌氟合剂静滴消除寒战有效率达96.6%,预防有效率94%。哌氟合剂加红外线热幅射保温均无寒战发生。     

Shivering and Shivering-like Tremor during Labor with and without Epidural Analgesia

Background: Effective treatment and prevention of hyperthermia and shivering-like tremor during labor is hindered by a poor understanding of their causes. The authors sought to identify the incidence of nonthermoregulatory shivering-like tremor and the factors associated with this activity.

Methods: The authors studied women in spontaneous fullterm labor who chose epidural analgesia (n = 21) or opioid sedation (n = 31). Shivering-like tremor and sweating were evaluated by observation. Core temperature was recorded in the external auditory canal using a compensated infrared thermometer. Arteriovenous shunt tone was evaluated with forearm minus fingertip skin temperature gradients; gradients less than 0 were considered evidence of vasodilation. Tremor was considered nonthermoregulatory when core temperature exceeded 37 [degree sign]C and the arms were vasodilated. Pain was evaluated using a visual analog scale.

Results: Shivering-like tremor was observed in 18% of 290, 30-min data-acquisition epoch before delivery. The patients were both normothermic and vasodilated during 15% of these epochs. Shivering was observed in 16% of 116 postdelivery epochs and was nonthermoregulatory in 28%. Sweating was observed in 30% of predelivery epochs, and the patients were both hypothermic and vasoconstricted during 12%. The mean core temperature in patients given epidural analgesia was approximately 0.2 [degree sign]C greater than in those given sedation. Hyperthermia was observed during 10 epochs (38.4 +/- 0.3 [degree sign]C) during epidural analgesia and during 10 epochs (38.4 +/- 0.3 [degree sign]C) with sedation. The patients were vasoconstricted in more than 50% of these epochs in each group. Multivariate mixed-effects modeling identified high pain scores and vasoconstriction as significant predictors of shivering. There were no predictors for shivering epochs in patients who were simultaneously normothermic and vasodilated. Significant predictors of sweating were time before delivery, high pain scores, hypothermia with vasoconstriction, high thermal comfort, and low mean skin temperature. There were no predictors for sweating epochs in patients who were simultaneously hypothermic and vasoconstricted.     

Population Pharmacokinetic-Pharmacodynamic Modeling of Epidural Anesthesia

Background: In previous studies, the authors reported on the absorption and disposition kinetics of levobupivacaine and ropivacaine. The current study was designed to develop a population pharmacokinetic-pharmacodynamic model capable of linking the kinetic data to the analgesic effects of these local anesthetics (i.e., sensory neural blockade).

Methods: A disposition compartmental model was fitted to concentration data of the intravenously administered deuterium-labeled anesthetics, and a model consisting of two parallel absorption compartments and the identified disposition compartments was fitted to concentration data of the concomitantly epidurally administered unlabeled anesthetics. The epidural segments were modeled by individual central and peripheral absorption compartments and effect sites, which were fitted to the simultaneously acquired pinprick data. A covariate model incorporated the effects of age.

Results: The threshold for epidural anesthesia increased from the lower to the higher segments. The central effect compartment equilibration half-lives were approximately 15 min for levobupivacaine and 25 min for ropivacaine. For levobupivacaine, age reduced the equilibration half-lives at all segments; for ropivacaine, age increased the anesthetic sensitivity at segments T12 and higher.     

PPH术中应用蛛网膜下腔麻醉与硬膜外麻醉的效果比较

为观察PPH术中应用蛛网膜下腔麻醉与硬膜外麻醉的效果,将行PPH治疗的重度痔患者80例随机分为对照组和观察组,每组40例.对照组患者采用蛛网膜下腔麻醉,观察组患者采用硬膜外麻醉,比较2组患者手术情况、麻醉感觉阻滞情况、麻醉效果、运动阻滞情况及不良反应.结果显示,2组患者手术情况、麻醉感觉阻滞情况比较差异无统计学意义(P...     

Changes of Electroencephalographic Bicoherence during Isoflurane Anesthesia Combined with Epidural Anesthesia

Background: The authors previously reported that, during isoflurane anesthesia, electroencephalographic bicoherence values changed in a fairly restricted region of frequency versus frequency space. The aim of the current study was to clarify the relation between electroencephalographic bicoherence and the isoflurane concentration.

Methods: Thirty elective abdominal surgery patients (male and female, aged 34-77 yr, American Society of Anesthesiologists physical status I-II) were enrolled. After electroencephalogram recording with patients in an awake state, anesthesia was induced with 3 mg/kg thiopental and maintained with oxygen and isoflurane. Continuous epidural anesthesia with 80-100 mg/kg 1% lidocaine was also administered. Using software they developed, the authors continuously recorded the FP1-A1 lead of the electroencephalographic signal and expired isoflurane concentration to an IBM-PC compatible computer. After confirming the steady state of each isoflurane (end-tidal concentration at 0.3, 0.5, 0.7, 0.9, 1.1, 1.3, and 1.5%), electroencephalographic bicoherence values were calculated.

Results: In a light anesthetic state, electroencephalographic bicoherence values were low (generally <= 15.0%). At increased concentrations of isoflurane, two peaks of electroencephalographic bicoherence emerged along the diagonal line (f1 = f2). The peak emerged at around 4.0 Hz and grew higher as isoflurane concentration increased until it reached a plateau (43.8 +/- 3.5%, mean +/- SD) at isoflurane 0.9%. The other peak, at about 10.0 Hz, also became significantly higher and reached a plateau (32.6 +/- 9.2%) at isoflurane 0.9%; at isoflurane 1.3%, however, this peak slightly decreased.