Skip Navigation LinksHome > February 2001 - Volume 94 - Issue 2 > Opioids Inhibit Febrile Responses in Humans, Whereas Epidura...
Anesthesiology:
Clinical Investigations

Opioids Inhibit Febrile Responses in Humans, Whereas Epidural Analgesia Does Not: An Explanation for Hyperthermia during Epidural Analgesia

Negishi, Chiharu M.D.*; Lenhardt, Rainer M.D.†; Ozaki, Makoto M.D.‡; Ettinger, Katharine B.A.§; Bastanmehr, Hiva B.S.§; Bjorksten, Andrew R. Ph.D.‖‖; Sessler, Daniel I. M.D.#

Free Access
Article Outline
Collapse Box

Author Information

Collapse Box

Abstract

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 μg/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°C · h on the control day, to 3.8 ± 3.0°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°C was halved by intravenous fentanyl, and the fraction exceeding 38.5°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.
HYPERTHERMIA frequently complicates epidural analgesia for labor and delivery 1–4 and after surgery in patients who are not pregnant. 5 A clinical consequence of this hyperthermia is that women given epidural analgesia are more often given antibiotics than in those treated conventionally, and their offspring are more commonly treated for sepsis. 2,6,7 However, a convincing cause for hyperthermia in association with epidural analgesia has yet to be proposed.
Implicit in all discussions of hyperthermia associated with epidural analgesia is the assumption that the technique causes hyperthermia. 8 It is important, however, to recognize that the “control” patients in these observational studies were not given a placebo. Instead, their pain was usually treated with opioids. This is a critical factor, because even low concentrations of intravenous opioids attenuate fever. 9 It thus seems likely that fever associated with infection, tissue injury, atelectasis, and so forth is suppressed by opioids in the “control patients,” whereas it is expressed normally in patients given epidural analgesia.
We therefore tested the hypothesis that fever in humans is manifested normally during ropivacaine epidural analgesia, but suppressed by low doses of the intravenous opioid fentanyl. Because fentanyl may also be given epidurally, we also evaluated the effects of combined ropivacaine–fentanyl epidural analgesia. Fever is mediated by peripheral release of endogenous pyrogens 10 such as the cytokines interleukin (IL) 6 or tumor necrosis factor (TNF) α. To identify a potential peripheral mechanism by which epidural analgesia may inhibit fever, we therefore simultaneously measured plasma cytokine concentrations.
Back to Top | Article Outline

Patients and Methods

With approval from the University of California, San Francisco, Committee of Human Research and informed consent, we studied eight healthy male volunteers, each on four study days. None was obese, was taking medication, or had a history of thyroid disease or Raynaud syndrome. Morphometric and demographic characteristics included: age, 27 ± 6 yr; height, 180 ± 8 cm; weight, 74 ± 8 kg; and body fat, 17 ± 5%.
The volunteers fasted for 8 h before arriving at the laboratory. They were minimally clothed and reclined on a standard operation table during the study. Ambient temperature was maintained near 22°C and relative humidity near 45%. To avoid circadian fluctuations, studies were scheduled at the same time each day.
An 18-gauge catheter was inserted in a left forearm vein for fluid and drug administration. Lactated Ringer’s solution at ambient temperature was infused at a rate of 100 ml/h. A 16-gauge catheter was inserted in the right median-cephalic vein for blood sampling.
Back to Top | Article Outline
Protocol
On each study day, the volunteers were randomly assigned to either: (1) a control day when no opioid or epidural analgesia was given; (2) epidural analgesia using 0.2% ropivacaine alone; (3) epidural analgesia using 0.2% ropivacaine in combination with 2.0 μg/ml fentanyl; or (4) intravenous fentanyl at a target plasma concentration of 2.5 ng/ml. Volunteers were then given an intravenous injection of 50 IU/g of human recombinant IL-2 (elapsed time, 0), observed 2 h later by 100 IU/g of the drug (Chiron, Inc., Berkeley, CA). At least 2 weeks were allowed between the fentanyl day and the combined epidural ropivacaine–fentanyl day to minimize tolerance.
On the epidural days, a catheter was inserted into the epidural space via the L2–L3 interspace. The epidural catheter was then injected with 2 ml lidocaine, 2%, with epinephrine 1:100,000. This test dose was followed in 5 min by 10–12 ml of 0.2% ropivacaine (Ropivacaine HCl; Astra, Inc., Westborough, MA) or ropivacaine in combination with 2 μg/ml fentanyl without epinephrine. The initial anesthetic dose was based on the volunteers’ heights and calculated to produce a dermatomal level of sensory blockade near T8–S1 bilaterally as determined by loss of cutaneous cold sensation and response to pinprick. Epidural analgesia was then maintained with the continuously administered drug at a rate of 8–12 ml/h to maintain the target sensory block level.
On the intravenous fentanyl day, fentanyl was administered using a pump (Ohmeda 9000; Ohmeda, Steeton, UK) programmed to target fentanyl blood concentrations of 2.5 ng/ml using a modification of the Kruger–Thiemer method 11 and published data. 12 This is a low concentration that produces only mild sedation and is similar to concentrations that may be used for labor or postoperative pain. 13,14 To maintain an appropriate end-tidal carbon dioxide tension (Pco2), the volunteers were reminded to breathe during fentanyl administration, and, if necessary, oxygen was given via nasal cannula to maintain oxygen saturation measured by pulse oximetry (Spo2) more than 95%. Fentanyl was infused for 8 h and then discontinued.
Back to Top | Article Outline
Measurements
Core temperature was measured at the tympanic membrane using Mon-a-Therm thermocouples (Mallinckrodt Anesthesiology Product, Inc., St. Louis, MO). Mean skin-surface temperature was calculated from measurements at 15 area-weighted sites. 15 Temperatures were recorded at every 5 min from thermocouples connected to Iso-Thermex thermometers having an accuracy of 0.1°C and a precision of 0.01°C (Columbus Instruments Corp., Columbus, OH).
Pupillary responses were measured to evaluate the pharmacodynamic effect of fentanyl. An infrared pupillometer (Fairville Medical Optics, Buckinghamshire, UK) was programmed to provide a 0.5-s, 130 candela/m2 pulse of green light and to scan the pupil at the rate of 10 Hz for 2 s from the beginning of the light stimulus. We have previously described this method 16 and used it to quantify opioid effect. 17 The maximum reduction in pupil size during the 2-s scan identified the reflex amplitude. Ambient light was maintained near 150 lux, and the contralateral eye was covered during measurements.
Peripheral venous blood for fentanyl analysis was sampled just before IL-2 administration and at 1, 3, 5, and 7 elapsed h. The plasma samples were stored at −20°C until analysis by gas chromatography, using techniques described by Bjorkman and Stanski 18 and Selinger et al. 19 The limit of detection is near 0.2 ng/ml.
We evaluated IL-6, IL-8, and TNF α, as well as the antiinflammatory cytokine IL-10 hourly. 20–23 Plasma IL-6 and IL-8 concentrations were measured by an enzyme-linked immunosorbent assay (Human interleukin-6 and interleukin-8 ELISA Kits; Toray Industries, Inc., Tokyo, Japan). TNF α concentrations were determined by a human immunoassay (Quantikine HS; R&D Systems, Minneapolis, MN). Plasma IL-10 concentrations were determined by a solid-phase enzyme-amplified immunoassay (IL-10 EASIA Kit; Medgenix Diagnostics S.A., Fleurus, Belgium). In each case, the assays were performed per the manufacturers’ directions, and appropriate calibration curves were constructed. All are highly specific and sensitive over the range of observed values.
Heart rates and arterial oxygen saturation were monitored continuously using pulse oximetry (Biox 3700; Ohmeda, Salt Lake City, UT). Blood pressure at the ankle was determined oscillometrically (Critikon, Tampa, FL). End-tidal carbon dioxide concentrations and respiratory rates were monitored using a Capnomac Ultima (Datex Medical Instruments, Tewksbury, MA). All temperatures and hemodynamic data were recorded at 5-min intervals.
Back to Top | Article Outline
Data Analysis
Febrile responses on each study day are presented as time-dependent changes. Specifically, we considered integrated core temperature, peak temperature, and the time-to-peak temperature. Values were integrated during 3–8 elapsed h, with respect to the mean temperature during the first elapsed hour. That is, we calculated the area under the temperature curve. This quantified the extent to which core temperature exceeded initial values (in °C · h) and is a standard way of expressing fever magnitude.
Ambient temperature and humidity, hemodynamic responses, end-tidal Pco2, respiratory rate, Spo2, and administered fluid volume on each study day were first averaged within each volunteer during 3–8 elapsed h; the resulting values were then averaged among volunteers.
Most results were compared using repeated-measures analysis of variance and Scheffé F test. Time-dependent changes were similarly evaluated. A chi-square analysis was used to evaluate the fraction of the temperature measurements in each group exceeding 38.0, 38.5, and 39.0°C. Results are presented as mean ± SD;P < 0.05 was considered statistically significant.
Back to Top | Article Outline

Results

Table 1
Table 1
Image Tools
The volunteers were only mildly sedated by intravenous fentanyl. Total plasma fentanyl concentrations during administration of fentanyl averaged 1.5 ± 0.2 ng/ml on the intravenous fentanyl day, but only 0.2 ± 0.1 ng/ml when fentanyl was given epidurally. Pupil size and reflex amplitude were significantly reduced by intravenous fentanyl (table 1). There were no significant differences in ambient temperature, relative humidity, heart rate, blood pressure, end-tidal Pco2, and Spo2 on the four study days.
Table 2
Table 2
Image Tools
Fig. 1
Fig. 1
Image Tools
Core temperatures peaked at 38.7 ± 0.6°C on the control day, at 38.7 ± 0.7°C during epidural ropivacaine, at 38.7 ± 0.9°C with combined epidural ropivacaine–fentanyl, but only at 38.1 ± 0.7°C during intravenous fentanyl (table 2). Fentanyl significantly reduced the febrile response to pyrogen, decreasing integrated core temperature from 7.0 ± 3.2°C · h on the control day to 3.8 ± 3.0°C · h on the intravenous fentanyl day. In contrast, epidural ropivacaine and epidural ropivacaine–fentanyl did not inhibit manifestation of fever (fig. 1).
Table 3
Table 3
Image Tools
The fraction of core-temperature measurements that exceeded 38°C was halved by intravenous fentanyl. The fraction of measurements exceeding 38.5°C was reduced more than fivefold by intravenous fentanyl (table 3). Both these reductions were statistically significant (P < 0.001).
Plasma concentration of TNF α, IL-6, and IL-8 increased later, reaching peak concentrations after 4 or 5 elapsed h. All subsequently decreased to near-baseline values by 8 or 9 elapsed h. In contrast, IL-10 continued to increase throughout the study period. None of the cytokine concentrations differed significantly on the four study days.
Back to Top | Article Outline

Discussion

Epidural analgesia is associated with a high incidence of hyperthermia, 1,5,8 which provokes expensive and invasive interventions. 6,7 Because passive hyperthermia and excessive heat production are unlikely causes, elevated body temperature in laboring and postoperative patients is presumably true fever resulting from infection, tissue damage atelectasis, and so forth. The conventional understanding is that hyperthermia associated with epidural analgesia in the same clinical situation is caused by epidural analgesia. However, this theory is inconsistent with our observation that epidural analgesia failed to influence febrile responses. Instead, our data suggest that fever is inhibited by opioid administration in the “control” subjects.
Although maximum and average core temperatures differed by less than 1°C when the volunteers were given fentanyl and epidural analgesia, integrated temperature was halved by low-dose fentanyl. More importantly, the fraction of core temperatures exceeding various temperatures was reduced by a factor of two to five. This is a critical outcome because temperatures exceeding specific values often trigger laboratory investigations for infection and even antibiotic administration. That intravenous fentanyl reduces the fraction of temperatures exceeding various threshold temperatures thus explains the high incidence of “fever work-ups” in laboring mothers and their children after epidural analgesia. 6,7 It is also consistent with the fact that there is no evidence whatsoever suggesting that these additional infection investigations were otherwise justified or in any way influenced outcome. 2
Published reports demonstrate a correlation between hyperthermia during epidural analgesia and clinical signs of infection. 24 There is also evidence that hyperthermia during epidural analgesia is highly associated with placental inflammation. 25 These authors concluded: “Epidural analgesia is associated with intrapartum fever, but only in the presence of placental inflammation. This suggests that the fever reported with epidural analgesia results from immune responses rather than the analgesia itself.” These results are consistent with our theory that hyperthermia during epidural analgesia is associated with inflammation (although not necessarily infection). Our results thus suggest that hyperthermia during epidural analgesia should be taken seriously and not considered a benign complication of the anesthetic technique per se. In contrast, threshold temperatures triggering investigations for infection should probably be reduced by approximately 0.5°C in patients given opioid analgesia.
Opioids are frequently administered epidurally because they augment analgesia with little respiratory compromise. 26 Relatively little opioid is required in the epidural space compared with intravenous administration, and the dose we used was typical. 26,27 Plasma fentanyl concentrations were six- to sevenfold lower after epidural than intravenous administration of the drug, which is consistent with the relatively small epidural dose. 28 Furthermore, pupil size and reflex amplitude (which are excellent measures of opioid effect) were essentially unchanged by epidural fentanyl. As may be expected from these data, epidural fentanyl had no detectable influence on the febrile response.
We have previously demonstrated that opioid-induced inhibition of fever is mediated centrally, rather than by a reduction in peripheral concentrations of pyrogens, when opioids are given after IL-2. 9 Our current results confirm this observation and extend it to the case in which opioids are given before induction of fever. Epidural analgesia did not inhibit fever and, not surprisingly, also failed to reduce circulating pyrogen concentrations.
We evaluated volunteers rather than patients. Responses under clinical circumstances are likely to differ somewhat. Nonetheless, it remains likely that the cause we propose for hyperthermia associated with epidural analgesia applies widely. Our theory does not exclude other causes of hyperthermia during epidural analgesia; it therefore remains likely that other yet-to-be-identified mechanisms also contribute.
In summary, the conventional assumption is that hyperthermia during epidural analgesia is caused by the technique. We tested an alternative theory that fever in humans is manifested normally during epidural analgesia, but suppressed by low-dose opioid. Intravenous fentanyl halved the febrile response to pyrogen, whereas epidural ropivacaine and epidural ropivacaine–fentanyl did not inhibit fever. These data support our proposed mechanism for hyperthermia during epidural analgesia and suggest that hyperthermia during epidural analgesia should thus be taken seriously and not considered a benign complication of the anesthetic technique per se.
Back to Top | Article Outline

References

1. Fusi L, Maresh MJA, Steer PJ, Beard RW: Maternal pyrexia associated with the use of epidural analgesia in labour. Lancet 1989; 1: 1250–2

2. Philip J, Alexander JM, Sharma SK, Leveno KJ, McIntire DD, Wiley J: Epidural analgesia during labor and maternal fever. A nesthesiology 1999; 90: 1271–5

3. Vinson DC, Thomas R, Kiser T: Association between epidural analgesia during labor and fever. J Fam Pract 1993; 36: 617–22

4. Macaulay JH, Mrcog KB, Steer PJ: Epidural analgesia in labor and fetal hyperthermia. Obstet Gynecol 1992; 80: 665–9

5. Bredtmann RD, Herden HN, Teichmann W, Moecke HP, Kniesel B, Baetgen R, Techklenburg A: Epidural analgesia in colonic surgery: Results of a randomized prospective study. Br J Surg 1990; 77: 638–42

6. Lieberman E, Lang JM, Frigoletto F, Richardson DK, Ringer SA, Cohen A: Epidural analgesia, intrapartum fever, and neonatal sepsis evaluation. Pediatrics 1997; 99: 415–9

7. Lieberman E, Cohen A, Lang J, Frigoletto F, Goetzl L: Maternal intrapartum temperature elevation as a risk factor for cesarean delivery and assisted vaginal delivery. Am J Public Health 1999; 89: 506–10

8. Frigoletto FD, Lieberman E, Lang JM, Cohen A, Barss V, Ringer S, Datta S: A clinical trial of active management of labor. N Engl J Med 1995; 333: 745–50

9. Negishi C, Kim J-S, Lenhardt R, Sessler DI, Ozaki M, Vuong K, Bastanmehr H, Bjorksten AR: Alfentanil reduces the febrile response to interleukin-2 in men. Crit Care Med 1999; 28: 1295–300

10. Davatelis G, Wolpe SD, Sherry B, Dayer JM, Chicheportiche R, Cerami A: Macrophage inflammatory protein-1: A prostaglandin-independent endogenous pyrogen. Science 1989; 243: 1066–8

11. Crankshaw DP, Karasawa F: A method for implementing programmed infusion of theiopentone and methohexitone with a simple infusion pump. Anaesth Int Care 1989; 17: 496–9

12. Scott JC, Ponganis KV, Stanski DR: EEG quantification of narcotic effect: The comparative pharmacodynamics of fentanyl and alfentanil. A nesthesiology 1985; 62: 234–41

13. Gourlay GK, Kowalski SR, Plummer JL, Cousins MJ, Armstrong PJ: Fentanyl blood concentration—Analgesic response relationships in the treatment of postoperative pain. Anesth Analg 1988; 67: 329–37

14. Lehmann K: Pharmacokinetics of opioid analgesics, Patient Controlled Analgesia. Edited by Harmer M, Rosen M, Vickers MD. Oxford, Blackwell Scientific, 1985, pp 18–29

15. Sessler DI, Schroeder M: Heat loss in humans covered with cotton hospital blankets. Anesth Analg 1993; 77: 73–7

16. Belani KB, Sessler DI, Larson M, Lopez M, Washington DE, Ozaki M, McGuire J, Merrifield B, Hynson J, Schroeder M: The pupillary light reflex: Effects of anesthetics and hyperthermia. A nesthesiology 1993; 79: 23–7

17. Kurz A, Ikeda T, Sessler DI, Larson M, Bjorksten AR, Dechert M, Christensen R: Meperidine decreases the shivering threshold twice as much as the vasoconstriction threshold. A nesthesiology 1997; 86: 1046–54

18. Bjorkman S, Stanski DR: Simultaneous determination of fentanyl and alfentanil in rat tissues by capillary column gas chromatography. J Chromatog 1988; 433: 95–104

19. Selinger K, Lanzo C, Sekut A: Determination of remifentanil in human and dog blood by HPLC with UV detection. J Pharm Biomed Anal 1994; 12: 243–8

20. de Waal Malefyt R, Haanen J, Spits H, Roncarolo MG, te Velde A, Figdor C, Johnson K, Kastelein R, Yssel H, de Vries JE: Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J Exp Med 1991; 174: 915–24

21. de Waal Malefyt R, Abrams J, Bennett B, Figdor CG, de Vries JE: Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: An autoregulatory role of IL-10 produced by monocytes. J Exp Med 1991; 174: 1209–20

22. Fiorentino DF, Zlotnik A, Mosmann TR, Howard M, O’Garra A: IL-10 inhibits cytokine production by activated macrophages. J Immunol 1991; 147: 3815–22

23. Nava F, Calapai G, Facciola G, Cuzzocrea S, Marciano MC, De Sarro A, Caputi AP: Effects of interleukin-10 on water intake, locomotory activity, and rectal temperature in rat treated with endotoxin. Int J Immunopharmacol 1997; 19: 31–8

24. Churgay CA, Smith MA, Blok B: Maternal fever during labor—what does it mean? J Am Board Fam Pract 1994; 7: 14–24

25. Dashe JS, Rogers BB, McIntire DD, Leveno KJ: Epidural analgesia and intrapartum fever: placental findings. Obstet Gynecol 1999; 93: 341–4

26. Scott DA, Blake D, Buckland M, Etches R, Halliwell R, Marsland C, Merridew G, Murphy D, Paech M, Schug SA, Turner G, Walker S, Huizar K, Gustafsson U: A comparison of epidural ropivacaine infusion alone and in combination with 1, 2, and 4 microg/mL fentanyl for seventy-two hours of postoperative analgesia after major abdominal surgery. Anesth Analg 1999; 88: 857–64

27. Liu SS, Moore JM, Luo AM, Trautman WJ, Carpenter RL: Comparison of three solutions of ropivacaine/fentanyl for postoperative patient-controlled epidural analgesia. A nesthesiology 1999; 90: 727–33

28. Baxter AD, Laganiere S, Samson B, Stewart J, Hull K, Goernert L: A comparison of lumbar epidural and intravenous fentanyl infusions for post-thoracotomy analgesia. Can Anaesth 1994; 41: 184–91

Cited By:

This article has been cited 13 time(s).

Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie
Chorioamnionitis, not epidural analgesia, is associated with maternal fever during labour
Vallejo, MC; Kaul, B; Adler, LJ; Phelps, AL; Craven, CM; Macpherson, TA; Sweet, RL; Ranianathan, S
Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie, 48(): 1122-1126.

Journal of Clinical Anesthesia
Activin beta A in term placenta and its correlation with placental inflammation in parturients having epidural or systemic meperidine analgesia: a randomized study
Evron, S; Parameswaran, R; Zipori, D; Ezri, T; Sadan, O; Koren, R
Journal of Clinical Anesthesia, 19(3): 168-174.
10.1016/j.jclinane.2006.10.013
CrossRef
Bjog-An International Journal of Obstetrics and Gynaecology
Maternal temperature during labour
Schouten, FD; Wolf, H; Smjt, BJ; Bekedam, DJ; de Vos, R; Wahlen, I
Bjog-An International Journal of Obstetrics and Gynaecology, 115(9): 1131-1137.
10.1111/j.1471-0528.2008.01781.x
CrossRef
Journal of Clinical Anesthesia
Fever, epidurals, and inflammation: a burning issue
Palanisamy, A; Hepner, DL; Segal, S
Journal of Clinical Anesthesia, 19(3): 165-167.
10.1016/j.jclinane.2007.01.008
CrossRef
Journal of Anesthesia
The effects of remifentanil or acetaminophen with epidural ropivacaine on body temperature during labor
Evron, S; Ezri, T; Protianov, M; Muzikant, G; Sadan, O; Herman, A; Szmuk, P
Journal of Anesthesia, 22(2): 105-111.
10.1007/s00540-007-0589-8
CrossRef
Journal of Clinical Anesthesia
Fever and infection during parturition: A preanesthetic or a postanesthetic problem?
Finster, M
Journal of Clinical Anesthesia, 15(6): 409-410.
10.1016/S0952-8180(03)00077-1
CrossRef
International Journal of Obstetric Anesthesia
The rise in maternal temperature associated with regional analgesia in labour is harmful and should be treated
Irestedtz, L
International Journal of Obstetric Anesthesia, 12(4): 284-286.
10.1016/S0959-289X(03)00048-7
CrossRef
Peptides
Endogenous opiates: 2000
Vaccarino, AL; Kastin, AJ
Peptides, 22(): 2257-2328.

Clinics in Perinatology
The Association Between Epidural Labor Analgesia and Maternal Fever
Arendt, KW; Segal, BS
Clinics in Perinatology, 40(3): 385-+.
10.1016/j.clp.2013.06.002
CrossRef
European Journal of Obstetrics & Gynecology and Reproductive Biology
Effects on fetal and maternal temperatures of paracetamol administration during labour: a case-control study
Lavesson, T; Akerman, F; Kallen, K; Olofsson, P
European Journal of Obstetrics & Gynecology and Reproductive Biology, 168(2): 138-144.
10.1016/j.ejogrb.2012.12.033
CrossRef
Anesthesiology
Differences in Systemic Opioid Use Do Not Explain Increased Fever Incidence in Parturients Receiving Epidural Analgesia
Gross, JB; Cohen, AP; Lang, JM; Frigoletto, FD; Lieberman, ES
Anesthesiology, 97(1): 157-161.

PDF (166)
Anesthesiology
Temperature Monitoring and Perioperative Thermoregulation
Sessler, DI
Anesthesiology, 109(2): 318-338.
10.1097/ALN.0b013e31817f6d76
PDF (737) | CrossRef
Anesthesiology
Pharmacokinetics of an Implanted Osmotic Pump Delivering Sufentanil for the Treatment of Chronic Pain
Fisher, DM; Kellett, N; Lenhardt, R
Anesthesiology, 99(4): 929-937.

PDF (430)
Back to Top | Article Outline

© 2001 American Society of Anesthesiologists, Inc.

Publication of an advertisement in Anesthesiology Online does not constitute endorsement by the American Society of Anesthesiologists, Inc. or Lippincott Williams & Wilkins, Inc. of the product or service being advertised.
Login

Article Tools

Images

Share