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Shivering and Neuraxial Anesthesia
Review Article
Shivering and Neuraxial Anesthesia Larry J. Crowley, M.B., M.R.C.P.I., F.C.A.R.C.S.I., and Donal J. Buggy, M.D., F.R.C.P.I., F.C.A.R.C.S.I., F.R.C.A. Shivering, which usually occurs as a thermoregulatory response to cold, may also occur following general or neuraxial anesthesia. Some of the causative factors of this type of shivering may be common to both, but some are particular to neuraxial anesthesia. Although shivering may have beneficial thermoregulatory effects, it places the body under increased physiological stress. In a broad sample of 21 studies, the median incidence of shivering related to neuraxial anesthesia in the control groups was 55%. Both pharmacological and nonpharmacological mechanisms have been found to be effective in reducing this shivering. This review aims to elucidate the mechanisms of the shivering that occurs during neuraxial anesthesia, and to examine strategies for prevention and treatment of this shivering. Reg Anesth Pain Med 2008;33:241-252. Key Words:
Epidural anesthesia, Spinal anesthesia, Shivering, Anesthesia side effects.
S
hivering may be defined as an involuntary, repetitive activity in skeletal muscles. Shivering usually occurs as a thermoregulatory response to cold, although nonthermoregulatory shivering may also occur. Core temperature in humans varies with circadian rhythm (and with menstrual cycle in females), but is normally maintained within the narrow range of 36.5°C to 37.0°C. Shivering may occur following general or neuraxial anesthesia, and undoubtedly some of the causative factors are common to both. However, as this review will demonstrate, some factors are particular to neuraxial anesthesia. This review aims to elucidate the mechanisms of the shivering that occurs during neuraxial anesthesia, and to examine strategies for prevention and treatment of this shivering.
Search Method An unlimited search of the PubMed database (extending from the 1950s) was conducted up to the end of October 2007 using the key phrases “shivering and epidural anesthesia” and “shivering and From the Department of Anesthesia, Intensive Care & Pain Medicine, Mater Misericordiae University Hospital, Dublin, Republic of Ireland. Accepted for publication November 20, 2007. Reprint requests: Larry J. Crowley, M.B., M.R.C.P.I., F.C.A.R.C.S.I., Department of Anesthesia, Intensive Care & Pain Medicine, Cork University Hospital, Cork, Republic of Ireland. E-mail: [email protected] © 2008 by the American Society of Regional Anesthesia and Pain Medicine. 1098-7339/08/3303-0001$34.00/0 doi:10.1016/j.rapm.2007.11.006
spinal anesthesia.” All retrieved articles were analyzed for information that was used to construct this review. The reference lists of retrieved articles and relevant review articles were also examined.
Incidence in Neuraxial Anesthesia The median incidence of shivering related to neuraxial anesthesia in the control groups of a broad sample of 21 studies is 55% (interquartile range of 40%-64%).1-21 Within these studies there is a heterogeneity of study populations, definition of shivering, study design, and research questions.
Adverse Effects of Shivering Although shivering may have beneficial thermoregulatory effects, it places the body under increased physiological stress, which may be deleterious.22 Shivering may double oxygen consumption and carbon dioxide production, although increase of the latter is typically much smaller.23,24 Plasma catecholamines and cardiac output increase in response to this physiological stress.25 Shivering movements during neuraxial anesthesia may interfere with monitoring of blood pressure, electrocardiogram, and pulse oximetry,26,27 as well as reducing patient comfort and satisfaction.28
Grading of Shivering Grading and definition of shivering are important to allow meaningful comparisons of interventions in this area. An attempt has been made to grade
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shivering on the following scale: 0, no shivering; 1, piloerection or peripheral vasoconstriction but no visible shivering; 2, muscular activity in only one muscle group; 3, muscular activity in more than one muscle group but not generalized shivering; and 4, shivering involving the whole body.29 An alternative, more user-friendly, scale specific for neuraxial anesthesia would be: 0, no shivering; 1, shivering not interfering with monitoring or causing patient distress; and 2, shivering interfering with patient monitoring or causing patient distress.
Mechanisms Neurophysiology Similar to other physiological systems, the human thermoregulatory system is often divided into 3 components: thermosensors and afferent neural pathways, a center for integration of this input, and effector pathways. Although incompletely understood, many of the neural pathways involved in thermoregulation have been elucidated and summarized elsewhere.30 A simplified schematic representation of the shivering pathway is illustrated in Figure 1. The lateral spinothalamic tract projects to the hypothalamic thermoregulatory centers and to nuclei within the reticular formation in the pons. The nucleus raphe magnus facilitates transmission of thermal information to the hypothalamus and has an inhibitory role in shivering. The locus subcoeruleus appears to have a predominantly excitatory role in shivering. The preoptic area of the anterior hypothalamus appears to be the central integrator of input. The efferent shivering pathway starts at an area between the anterior and posterior hypothalamus and makes
Fig 1. Schematic diagram of the shivering pathway.
multiple connections within the reticular formation before it ends at the ␣ motor neurons. Thermoregulation Undoubtedly, shivering occurs primarily in response to core hypothermia. The normal response to hypothermia involves thermoregulatory vasoconstriction to decrease cutaneous heat loss, and maintain heat within the core. Maximal vasoconstriction usually occurs before thermoregulatory shivering occurs. When the core temperature decreases to a certain point, known as the shivering threshold, thermoregulatory shivering then occurs. The threshold temperature at which shivering occurs may be lower in males relative to females, and may also decrease with age.31,32 A decrease in core temperature (measured at the tympanic membrane) of 0.5°C is sufficient to induce shivering in nonpregnant volunteers undergoing epidural anesthesia.33 The shivering that occurs during epidural anesthesia is accompanied by central hypothermia and peripheral vasoconstriction above the level of the block, and is thus primarily normal thermoregulatory shivering.33 The normal response to warming of the legs is a reduction of the shivering threshold.34 Hynson et al. demonstrated that core hypothermia during the first hour of epidural anesthesia does not result from heat loss to the environment in excess of metabolic heat production, but rather from redistribution of core body heat to the peripheral tissues.35 Matsukawa et al. demonstrated that the magnitude of this decrease for epidural anesthesia was 0.8°C ⫾ 0.3°C in the first hour, and a further 0.4°C ⫾ 0.3°C in the subsequent 2 hours, as well as confirming that redistribution of heat from the core to the periphery is responsible for this decrease.36 Neuraxial block results in impairment of autonomic thermoregulation below the level of the block. The vasodilatation that occurs below the level of a neuraxial block is presumably responsible for this redistribution of heat. One might expect a greater degree of vasodilatation (and thus decrease in core temperature) following spinal block. Saito et al. demonstrated that for the first 30 minutes of anesthesia, core temperature decreased significantly faster in patients given spinal block when compared with those given epidural block. After 30 minutes, core temperatures decreased at identical rates during epidural and spinal anesthesia, with the end result being lower core temperature in the spinal group.13 Thus one might expect higher rates of shivering with spinal block compared with epidural block, but as discussed below, this does not appear to be the case.
Shivering and Neuraxial Anesthesia
Epidural Versus Spinal Studies comparing the incidence of shivering for epidural versus spinal anesthesia are lacking, although the intensity of shivering seems to be greater during epidural anesthesia.13 Neuraxial anesthesia will block all thermal sensations, but at typical ambient temperatures, is likely to block tonically-firing cold thermoreceptors more than warm thermoreceptors.37 Epidural anesthesia increases the apparent leg temperature (as distinguished from the actual leg temperature) perceived by the body, and this results in a decreased shivering threshold.38 Spinal anesthesia decreases the shivering threshold in direct relation to the number of dermatomes blocked, i.e., less shivering with increased block height.39 To better understand the mechanisms of shivering during neuraxial anesthesia, it is important to try to explain the observed differences between epidural and spinal anesthesia. Spinal anesthesia usually results in complete block of all neurons below a certain level, whereas epidural anesthesia may result in a segmental block that often fails to block sacral dermatomes. Thus, for a given block height, block of thermal input during epidural anesthesia may be reduced relative to spinal anesthesia. This may result in less of a decrease in the shivering threshold relative to spinal anesthesia, and provide a possible explanation as to why shivering appears to be more intense following epidural block. Perhaps the simplest explanation for the apparent difference is the greater intensity of motor block with subarachnoid block compared with that in epidural block, such that patients are actually unable to shiver during subarachnoid block. It is unclear whether epidural or spinal block affect the shivering threshold in different ways. Saito et al., studying 30 parturients having elective cesarean delivery with epidural or spinal anesthesia, demonstrated a higher shivering threshold when using epidural anesthesia.13 In contrast, Ozaki et al., studying 7 male volunteers, failed to show a difference in shivering thresholds for epidural versus spinal anesthesia.40 It is theoretically possible that there are different thermoreceptors and mechanisms within the spinal cord compared with those within the epidural space. Temperature of Administered Fluid It has long been known that the spinal cord has thermoreceptors and is involved in thermoregulation.41 Administration of cold fluids into the epidural space may result in cooling of large epidural veins, which in turn communicate with the basal sinuses. This might also provide an explanation for the apparent difference in shivering intensity for
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epidural and spinal anesthesia. There seems to be some evidence that the temperature of epidural injectate may influence shivering. Ponte et al. found a statistically significant different incidence of shivering when studying 40 patients having elective cesarean delivery and epidural anesthesia. Shivering occurred in 9 of 20 who received epidural bupivacaine at 4°C, compared with 2 of 20 who received epidural bupivacaine at 37°C.42 Shehabi et al. demonstrated a similar reduction in shivering for patients receiving epidural bupivacaine warmed to 36.3°C, compared with bupivacaine at room temperature (22.3°C).6 In a study by Walmsley et al., 30 patients having postpartum tubal ligation received epidural bupivacaine at 4°C, with shivering occurring in 14 of 30 (47%). Eight of the 14 had “marked shivering” and then received further epidural bupivacaine at 41°C, whereupon shivering ceased in 4 of the 8 (50%).43 Two subsequent studies (on volunteers) failed to demonstrate that epidural injectate temperature influences the incidence of shivering, although both studies had small sample size.33,44 It is unknown whether or not the temperature of intrathecal injectate influences shivering. The temperature of intravenous fluids may also contribute to shivering. Workhoven et al., studying 44 parturients having elective cesarean delivery and epidural anesthesia, demonstrated that shivering occurred in 14 of 22 who received room temperature (20°C22.2°C) intravenous crystalloid. This compared with only 3 of 22 who received warmed (30°C33.9°C) intravenous fluids.3 General Versus Neuraxial Although the pathophysiological mechanisms of shivering during general anesthesia and neuraxial anesthesia are intertwined, there are subtle differences. For both, significant vasodilatation that results in heat loss may result in thermoregulatory shivering. During general anesthesia, normal thermoregulatory mechanisms are impaired by incompletely understood mechanisms, and thus shivering usually occurs only on awakening. Segmental block of neural input during neuraxial anesthesia constitutes a unique causative mechanism and also allows a degree of compensatory vasoconstriction and shivering above the level of the block. General and neuraxial anesthesia have distinct effects on the release of stress hormones, metabolic heat production, and transmission along pain pathways; all of which may have differing effects on thermoregulation and shivering. Electromyographic studies of shivering, using isoflurane anesthesia in volunteers (not undergoing surgery), revealed that shivering is composed of 2 distinct patterns of muscular activity: a
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tonic pattern with 4 to 10 cycles per minute, resembling normal thermoregulatory shivering, and a clonic pattern of 5 to 7 cycles per second, consistent with uninhibited spinal reflexes.45 It was also demonstrated that deep tendon reflexes are significantly exaggerated by central hypothermia. Analysis of electromyographic patterns of shivering, following epidural anesthesia in nonpregnant volunteers, revealed the tonic pattern of normal thermoregulatory shivering but failed to demonstrate any clonic tremor pattern.35 Pregnancy Many of the studies on shivering feature parturients having labor epidural analgesia or cesarean delivery with epidural or spinal anesthesia. Although there are no studies comparing shivering in this group versus males or nonpregnant females, the median incidence in published studies for this group is 52.5% (interquartile range of 36%-71%).2,4,6-8,10,11,13,14,17,18,21 This occurs despite the increase in temperature that normally occurs during labor,46 and the increase in temperature associated with epidural analgesia.47,48 A review of the hyperthermia related to labor epidural analgesia (and the associated shivering) offered many theories as to its causation, but it remains something of an anomaly.49 Indeed it is possible that shivering during labor (with or without neuraxial anesthesia) may be a phenomenon different than thermoregulatory shivering in a non-pregnant population. Shivering that occurs in the context of hyperpyrexia will lead to a further increase in temperature. It is known that the shivering threshold varies with gender, with females shivering at a higher threshold temperature relative to males.31 The influence of hormonal changes during pregnancy on shivering is unknown. Thermoregulatory shivering may occur in up to 14.5% of laboring women even before epidural block.2 Shivering during epidural block is more common among parturients who shiver prior to institution of epidural block, and in those who receive nitrous oxide.2 It has long been hypothesized that the shivering that occurs in the peripartum period may be an immunological result of fetomaternal transfusion.50,51 Nonthermoregulatory shivering also occurs in parturients with labor epidural analgesia.52 Opioids Opioid peptides have varying effects on body temperature.53 Intrathecal and epidural opioids commonly cause a small decrease in core temperature.54-56 One might expect increased shivering to occur as a result. However as discussed below, ad-
ministration of opioids plays a significant role in the prevention and treatment of shivering.
Prevention and Treatment Nonpharmacological Measures The redistribution of heat from the core to peripheral tissues, which occurs during neuraxial anesthesia, may cause hypothermia, which in turn may result in thermoregulatory shivering. By warming the peripheries, it should be possible to reduce this temperature gradient, and thus reduce shivering. Glosten et al. prewarmed volunteers for 2 hours, using a forced-air warming mattress set to 38°C, before performing epidural block. They demonstrated significantly higher skin temperatures, smaller decrease in core temperature, and reduced incidence of shivering, when compared with unwarmed volunteers.57 Horn et al. prewarmed parturients, who were having elective cesarean delivery with epidural anesthesia, for 15 minutes using a forced-air warming cover set to 43°C, and demonstrated significantly higher core temperatures, and less shivering in the prewarmed group. Interestingly, they also demonstrated that babies of prewarmed mothers had significantly higher rectal temperatures (37.1°C ⫾ 0.5°C vs. 36.2°C ⫾ 0.6°C), and umbilical vein pH (7.32 ⫾ 0.07 vs. 7.24 ⫾ 0.07).14 In contrast, application of an intraoperative forced-air warmer to the lower body of parturients having elective cesarean delivery and spinal anesthesia did not prevent intraoperative hypothermia or shivering.21 In this study, shivering was not the primary outcome, and thus the sample size may have been inadequate to demonstrate a difference. The application of a forced-air warmer to those with established shivering following general anesthesia was also not beneficial.58 Using an aluminum space blanket, in parturients having labor epidural analgesia, Buggy and Gardiner reduced the intensity of shivering, but failed to increase skin temperature, and thus failed to reduce the incidence of shivering.10 Wrapping of the legs in elastic bandages did not decrease the incidence of shivering in parturients having cesarean delivery with epidural anesthesia.17 Pharmacological Measures Much work has been done to examine the effects of multiple pharmacological agents on thermoregulation and shivering. Many of the studied agents have analgesic and sedative properties, and probably influence thermoregulation via effects on neurotransmission and neuronal receptors. Agents usually mediate effects via one or more of the
Table 1. Pharmacological Agents Used in the Prevention and Treatment of Neuraxial Anesthesia Shivering Agent (Pharmacology)
Dose
Route
Study Population
Number of Subjects
Time of Administration
32 Treatment; 48 control
Epidural initiation
Significantly decreased
None
Labor epidural analgesia
32 Treatment; 29 control
Established shivering
Significantly decreased
None
Juneja60
Male, urological surgery, spinal anesthesia Knee arthroscopy, spinal anesthesia Labor epidural analgesia and epidural for cesarean delivery Extracorporeal shock lithotripsy, epidural anesthesia Labor epidural analgesia
48 Treatment; 52 control
90 Minutes before spinal
Significantly decreased
Not mentioned
Mao61
50 Treatment; 50 control
Spinal initiation
Significantly decreased
None
Sia12
20 Treatment; 20 control
Established shivering
Decreased; significance unknown
Hypotension with 90 mcg
20 Treatment; 20 control
20 Minutes before epidural
Significantly decreased
Drowsiness
Yang9
20 Treatment; 20 control
Established shivering post delivery
Significantly decreased
Mercadante63*
50 Treatment; 50 control
5 Minutes before spinal
Significantly decreased
Decreased heart rate and blood pressure; increased drowsiness Sedation
50 Treatment; 50 control
Spinal initiation
No change
None
Jeon19†
31 Treatment; 38 control
Established working epidural
Significantly decreased
Increased sedation
Buprenorphine (mixed ,␦, and opioid agonist/antagonist) 0.3 mg Epidural Labor epidural analgesia
Butorphanol ( agonist and competitive antagonist) 1 mg Epidural Clonidine (␣2 agonist) 150 mcg
Oral
Intravenous
150 mcg
Intravenous
150 mcg
Intravenous
1 mcg/kg
Intravenous
150 mcg
Intrathecal
4.5 mcg/mL (median dose 28 mcg/hour)
Patient-controlled epidural analgesia
Orthopedic surgery, spinal anesthesia Orthopedic surgery, spinal anesthesia Labor epidural analgesia
German language; unknown sample size calculation.
75% success with 30 mcg; crossover design.
Report First Author
Lehmann59
Capogna62
Jeon19†
Shivering not primary outcome measure.
Paech64
Crowley and Buggy
30 mcg bolus every 5 minutes to maximum of 90 mcg
Notes
•
Intravenous
Side Effects
Shivering and Neuraxial Anesthesia
1 mcg/kg
Incidence of Shivering
245
246
Agent (Pharmacology)
Dose
Route
Study Population
Number of Subjects
Time of Administration
Incidence of Shivering
Side Effects
Notes
Report First Author
Fentanyl ( agonist) 25 mcg
Epidural
50 mcg
Epidural
25 mcg
Epidural
100 mcg bolus and 50 mcg/ hour infusion
Epidural
20 mcg
Intrathecal
Elective cesarean delivery, spinal anesthesia
Intravenous
Urological surgery, spinal anesthesia
Granisetron (5-HT3 antagonist) 3 mg
Labor epidural analgesia and epidural for cesarean delivery Labor epidural analgesia Elective cesarean delivery, epidural anesthesia Male, extracorporeal shockwave lithotripsy, epidural anesthesia
Established shivering
Significantly decreased
Nausea/vomiting
21 Treatment; 20 control 18 Treatment; 23 control
Epidural initiation
Significantly decreased Significantly decreased
Not mentioned Nonsignificant increase in nausea/vomiting
Papavertum, metoclopramide for some patients.
Liu8
Total of 14 patients, number in each group not recorded; no control 30 Treatment; 30 control
Epidural initiation
Shivering threshold significantly decreased in fentanyl group
Not mentioned
Significantly more intravenous fluid in fentanyl group.
Wheelahan66
At spinal initiation
Statistically significant decrease
Not significant
40 Treatment; 40 control
At spinal initiation
Decreased but significance not analyzed
Hypotension in 8, and nausea and vomiting in 1, of 40 subjects in treatment group; significance unknown
Baseline axillary and core temperature significantly different among groups; metoclopramide given to some patients.
Sagir20‡
At spinal initiation
Statistically significant decrease
Hypotension in 3 of 40 subjects in ketamine group
Group of ketamine 0.25 mg/kg with granisetron 1.5 mg also decreased shivering but significance not analyzed.
Sagir20‡
Ketamine (NMDA agonist, stimulates sympathetic nervous system, ␦ and agonist, antagonist) 0.5 mg/kg Intravenous Urological 40 Treatment; surgery, 40 control spinal anesthesia
Epidural initiation
Heterogeneous group; some patients shivering before epidural; use of nitrous oxide.
Matthews65
20 Treatment; 21 control
Shehabi6
Techanivate67
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Table 1. (Continued)
Table 1. (Continued) Agent (Pharmacology)
Dose
Route
Study Population
Number of Subjects
Time of Administration
Meperidine ( and ␣2 agonist, NMDA antagonist, inhibits 5-HT and norepinephrine uptake, antimuscarinic) 25 mg Epidural Labor epidural 11 Treatment; Established analgesia 11 control shivering
Elective cesarean delivery, epidural anesthesia Extracorporeal shockwave lithotripsy, epidural anesthesia
Intravenous
50 mg
Intravenous
Labor epidural analgesia
50 mg
Intravenous
0.5 mg/kg
Intravenous
Cesarean delivery, epidural anesthesia Cesarean delivery, epidural anesthesia
0.4 mg/kg
Intravenous
10 mg
Intrathecal
0.2 mg/kg
Intrathecal
Elective orthopedic surgery, spinal anesthesia Elective cesarean delivery, combined spinalepidural Nonemergent cesarean delivery, spinal anesthesia
Not significant
Nitrous oxide and intramuscular meperidine also used.
Report First Author
Brownridge2
47 Treatment; 47 control
Epidural initiation
Significantly decreased
Not significant
Sutherland7
19 Treatment (12.5 mg) and 21 treatment (25 mg); 20 control 20 Treatment; 20 control
15 to 30 minutes before epidural initiation
Nonsignificant trend to decrease for both doses
Not mentioned
Harris5
Established shivering post delivery
Significantly decreased
Mercadante63*
20 Treatment; 20 control
Established shivering
Significantly decreased
Decreased heart rate and increased drowsiness Increased drowsiness
15 Treatment, other treatment groups of amitriptyline and tramadol; no control 25 Treatment; 25 control
Established shivering
Significantly decreased compared with amitriptyline group
Increased somnolence
Tsai68§
At spinal initiation
Significantly decreased
None
Kelsaka69储
30 Treatment; 30 control
At spinal initiation
Significantly decreased
Not significant
20 Treatment; 20 control
At spinal initiation
Significantly decreased
Not significant
Casey4
Intravenous diphenhydramine and metoclopramide to some patients.
Hong70
Roy18
Crowley and Buggy
12.5 or 25 mg
Significantly decreased
Notes
•
Epidural
Side Effects
Shivering and Neuraxial Anesthesia
25 mg
Incidence of Shivering
247
248
Agent (Pharmacology)
Dose 25 mg
Route
Lower abdominal/ extremity surgery, spinal anesthesia Nefopam (inhibits uptake of 5-HT, norepinephrine, and dopamine) 0.15 mg/kg Intravenous Orthopedic surgery, epidural or spinal anesthesia Neostigmine (anticholinesterase) 75, 150, or Epidural Elective 300 mcg cesarean delivery, combined spinalepidural anesthesia Ondansetron (5-HT3 antagonist) 8 mg Intravenous Elective orthopedic surgery, spinal anesthesia
Sufentanil ( agonist) 0, 25, 50, 75, or 100 mcg
Intramuscular
Study Population
Epidural
Number of Subjects
Time of Administration
Incidence of Shivering
Side Effects
Notes
Report First Author
30 Treatment; 30 control
15 Minutes before spinal
Significantly decreased
Not mentioned
Chinese language.
Hu71
30 Treatment; 30 control
At induction of anesthesia
Significantly decreased
Nausea, vomiting, sweating; unknown significance
Nefopam significantly better than tramadol.
Bilotta16¶
20 Treatment for each dose; 20 control
Post cord clamping
Significantly increased with 300 mcg
Increased sedation
Unknown incidence of shivering at cord clamping; shivering not primary outcome.
Kaya72
25 Treatment; 25 control
At spinal initiation
Significantly decreased
Statistically significant bradycardia
Similar effectiveness for meperidine 0.4 mg/kg and ondansetron 8 mg, but not an equivalence study.
Kelsaka69储
Established shivering
Decreased when dose ⬎50 mcg; significance unknown
Not mentioned
0.2 mcg epidural epinephrine given to some patients.
Burks53
Established shivering
Significant decrease in time to stop shivering Significantly decreased
Increased nausea/ vomiting
Japanese language.
Chen73
Not significant
No difference in response rate or side effects for both doses.
Chan74
Elective 40 Treatment; repeat No control cesarean delivery, epidural anesthesia Tramadol (opioid agonist, inhibits reuptake of 5-HT, norepinephrine, and dopamine) 1 mg/kg Intravenous Nonparturients, 30 Treatment; epidural 30 control anesthesia 0.25 mg/kg Intravenous Elective or 13 Treatment or 0.5 mg/kg emergency (0.25 mg/ cesarean kg) and 12 delivery, treatment epidural (0.5 mg/ anesthesia kg); 11 control
Established shivering
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Table 1. (Continued)
Tsai68§
Bilotta16¶
Not significant
Nausea, vomiting, sweating; unknown significance Significantly decreased At induction of anesthesia
Significantly decreased compared with amitriptyline group Established shivering
*Same study. †Same study. ‡Same study. §Same study. 储Same study. ¶Same study.
Male and female, orthopedic surgery, epidural or spinal anesthesia Intravenous 0.5 mg/kg
Crowley and Buggy
249
Future Directions
15 Treatment, other treatment groups of amitriptyline and meperidine; no control 30 Treatment; 30 control Intravenous 0.5 mg/kg
Cesarean delivery, epidural anesthesia
Side Effects Incidence of Shivering Time of Administration Number of Subjects Study Population Route Dose Agent (Pharmacology)
Table 1. (Continued)
•
cholinergic, cationic, endogenous peptide, monoamine, N-methyl-D-aspartate, and serotonergic systems. Thermomodulation may occur, at peripheral receptors, at spinal cord level, or centrally, with some agents undoubtedly acting at multiple sites and at multiple receptors. Agents may also demonstrate differing effects depending on the route of administration. This complexity is reflected by the multitude of agents whose effects on thermoregulation and shivering following general anesthesia have been studied.30 Table 1 details studies on pharmacological agents whose effects on the shivering specific to neuraxial anesthesia have been examined.
Notes
Report First Author
Shivering and Neuraxial Anesthesia
The exact mechanisms underlying the observed differences in the intensity of shivering for epidural anesthesia and spinal anesthesia remain incompletely understood. It is also unclear whether or not epidural and spinal block affect thermoregulation to the same extent for a similar block height. Parturients may represent a special group, and the effects (if any) of thermomodulation on the fetus are unknown. It is unknown whether the choice of local anesthetic compound affects the incidence of shivering, although it has been speculated that shivering may occur more frequently when bupivacaine is used for epidural anesthesia.75 The shivering that occurs during general anesthesia and neuraxial anesthesia share some common pathways. Thus, it seems likely that agents that have proven successful in the treatment of shivering following general anesthesia, e.g., doxapram,76 ketanserin,77 physostigmine,78 and propofol,79 might also be useful in the management of shivering during neuraxial anesthesia. Any agent that interacts with neurotransmission, in particular via the dopaminergic and serotonergic pathways, is likely to have effects on thermoregulation, and possibly on shivering. A possible role exists for vasoconstrictor agents, which may reduce the loss of heat from the core to peripheral tissues. Exogenous intravenously administered prostaglandin E1 has been shown to reduce peripheral blood flow, temperature, and shivering.80 This raises questions about the potential effects of nonsteroidal anti-inflammatory drugs on thermoregulation. The intravenous administration of amino acid mixtures prevents the hypothermia that occurs during spinal anesthesia, which may have positive affects on blood loss and the incidence of shivering.81,82 As Table 1 demonstrates, many pharmacological agents reduce the incidence of shivering. However, it still remains unclear which agents may be most effective with the lowest inci-
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Table 2. Suggested Strategies to Prevent and Treat Neuraxial Anesthesia Shivering Prevention Pre-warm patient with a forced air warmer for at least 15 minutes.14 Avoid administration of cold epidural and intravenous fluids.3,6,42,43 Intrathecal fentanyl 20 mcg.67 Intrathecal meperidine 0.2 mg/kg or 10 mg.18,70 Intravenous ondansetron 8 mg.69 Epidural fentanyl 25 mg or 50 mg.6,8 Epidural meperidine 25 mg.7 Treatment Intravenous meperidine 50 mg.4,63 Intravenous tramadol 0.25 mg/kg or 0.5 mg/kg or 1 mg/kg.73,74 Intravenous clonidine 30, 60, 90 or 150 mcg.62,63
dence of side effects. We require further good quality, prospective, randomized trials of adequate sample size, comparing the effects of an intervention versus control on neuraxial shivering, where this shivering is defined or graded, and, is the primary outcome measure.
Conclusion Shivering that occurs due to neuraxial anesthesia is relatively common, and incompletely understood (particularly in the parturient). It is likely that any factor that causes core hypothermia may result in thermoregulatory shivering. The shivering threshold may also be altered by many factors, e.g., the level and type of block, and a multitude of pharmacological agents. The interplay between these known and unknown factors determines whether shivering occurs. As this review has demonstrated, there are effective pharmacological and nonpharmacological mechanisms to reduce the incidence of this shivering. Unfortunately, the heterogeneity of study populations and design make it difficult to apply strict evidence-based principles to the problem. Table 2 provides a suggested strategy for the prevention and treatment of neuraxial shivering, based on the authors’ opinions regarding ease of application, the number and quality of published studies, and the likelihood of side effects. We must always remember that shivering is usually a normal thermoregulatory response to a potentially harmful decrease in core temperature. Thus, if we apply mechanisms to reduce this shivering, we must ensure that we are adequately monitoring patient temperature and supplying adequate heat to our patients.
Acknowledgments The authors thank Drs. Joanne Douglas and Roanne Preston for advice and guidance.
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35. Hynson JM, Sessler DI, Glosten B, McGuire J. Thermal balance and tremor patterns during epidural anesthesia. Anesthesiology 1991;74:680-690. 36. Matsukawa T, Sessler DI, Christensen R, Ozaki M, Schroeder M. Heat flow and distribution during epidural anesthesia. Anesthesiology 1995;83:961-967. 37. Kurz A, Sessler DI, Schroeder M, Kurz M. Thermoregulatory response thresholds during spinal anesthesia. Anesth Analg 1993;77:721-726. 38. Emerick TH, Ozaki M, Sessler DI, Walters K, Schroeder M. Epidural anesthesia increases apparent leg temperature and decreases the shivering threshold. Anesthesiology 1994;81:289-298. 39. Leslie K, Sessler DI. Reduction in the shivering threshold is proportional to spinal block height. Anesthesiology 1996;84:1327-1331. 40. Ozaki M, Kurz A, Sessler DI, Lenhardt R, Schroeder M, Moayeri A, Noyes KM, Rotheneder E. Thermoregulatory thresholds during epidural and spinal anesthesia. Anesthesiology 1994;81:282-288. 41. Cabanac M. Temperature regulation. Annu Rev Physiol 1975;37:415-439. 42. Ponte J, Collett BJ, Walmsley A. Anaesthetic temperature and shivering in epidural anaesthesia. Acta Anaesthesiol Scand 1986;30:584-587. 43. Walmsley AJ, Giesecke AH, Lipton JM. Contribution of extradural temperature to shivering during extradural anaesthesia. Br J Anaesth 1986;58:1130-1134. 44. Ponte J, Sessler DI. Extradurals and shivering: Effects of cold and warm extradural saline injections in volunteers. Br J Anaesth 1990;64:731-733. 45. Sessler DI, Rubinstein EH, Moayeri A. Physiologic responses to mild perianesthetic hypothermia in humans. Anesthesiology 1991;75:594-610. 46. Marx GF, Loew DA. Tympanic temperature during labour and parturition. Br J Anaesth 1975;47:600602. 47. Fusi L, Steer PJ, Maresh MJ, Beard RW. Maternal pyrexia associated with the use of epidural analgesia in labour. Lancet 1989;1:1250-1252. 48. Camann WR, Hortvet LA, Hughes N, Bader AM, Datta S. Maternal temperature regulation during extradural analgesia for labour. Br J Anaesth 1991;67: 565-568. 49. Mercier FJ, Benhamou D. Hyperthermia related to epidural analgesia during labor. Int J Obstet Anesth 1997;6:19-24. 50. Goodlin RC, O’Connell LP, Gunthe RE. Childbirth chills: Are they an immunological reaction? Lancet 1976;2:79-80. 51. Ravid D, Gidoni Y, Bruchim I, Shapira H, Fejgin MD. Postpartum chills phenomenon: Is it a feto-maternal transfusion reaction? Acta Obstet Gynecol Scand 2001; 80:149-151. 52. Panzer O, Ghazanfari N, Sessler DI, Yucel Y, Greher M, Akca O, Donner A, Germann P, Kurz A. Shivering and shivering-like tremor during labor with and without epidural analgesia. Anesthesiology 1999;90: 1609-1616. 53. Burks TF. Opioids and opioid receptors in thermoregulation. In: Schonbaum E, Lomax P, eds. Thermo-
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Shivering and Neuraxial Anesthesia Larry J. Crowley, M.B., M.R.C.P.I., F.C.A.R.C.S.I., and Donal J. Buggy, M.D., F.R.C.P.I., F.C.A.R.C.S.I., F.R.C.A. Shivering, which usually occurs as a thermoregulatory response to cold, may also occur following general or neuraxial anesthesia. Some of the causative factors of this type of shivering may be common to both, but some are particular to neuraxial anesthesia. Although shivering may have beneficial thermoregulatory effects, it places the body under increased physiological stress. In a broad sample of 21 studies, the median incidence of shivering related to neuraxial anesthesia in the control groups was 55%. Both pharmacological and nonpharmacological mechanisms have been found to be effective in reducing this shivering. This review aims to elucidate the mechanisms of the shivering that occurs during neuraxial anesthesia, and to examine strategies for prevention and treatment of this shivering. Reg Anesth Pain Med 2008;33:241-252. Key Words:
Epidural anesthesia, Spinal anesthesia, Shivering, Anesthesia side effects.
S
hivering may be defined as an involuntary, repetitive activity in skeletal muscles. Shivering usually occurs as a thermoregulatory response to cold, although nonthermoregulatory shivering may also occur. Core temperature in humans varies with circadian rhythm (and with menstrual cycle in females), but is normally maintained within the narrow range of 36.5°C to 37.0°C. Shivering may occur following general or neuraxial anesthesia, and undoubtedly some of the causative factors are common to both. However, as this review will demonstrate, some factors are particular to neuraxial anesthesia. This review aims to elucidate the mechanisms of the shivering that occurs during neuraxial anesthesia, and to examine strategies for prevention and treatment of this shivering.
Search Method An unlimited search of the PubMed database (extending from the 1950s) was conducted up to the end of October 2007 using the key phrases “shivering and epidural anesthesia” and “shivering and From the Department of Anesthesia, Intensive Care & Pain Medicine, Mater Misericordiae University Hospital, Dublin, Republic of Ireland. Accepted for publication November 20, 2007. Reprint requests: Larry J. Crowley, M.B., M.R.C.P.I., F.C.A.R.C.S.I., Department of Anesthesia, Intensive Care & Pain Medicine, Cork University Hospital, Cork, Republic of Ireland. E-mail: [email protected] © 2008 by the American Society of Regional Anesthesia and Pain Medicine. 1098-7339/08/3303-0001$34.00/0 doi:10.1016/j.rapm.2007.11.006
spinal anesthesia.” All retrieved articles were analyzed for information that was used to construct this review. The reference lists of retrieved articles and relevant review articles were also examined.
Incidence in Neuraxial Anesthesia The median incidence of shivering related to neuraxial anesthesia in the control groups of a broad sample of 21 studies is 55% (interquartile range of 40%-64%).1-21 Within these studies there is a heterogeneity of study populations, definition of shivering, study design, and research questions.
Adverse Effects of Shivering Although shivering may have beneficial thermoregulatory effects, it places the body under increased physiological stress, which may be deleterious.22 Shivering may double oxygen consumption and carbon dioxide production, although increase of the latter is typically much smaller.23,24 Plasma catecholamines and cardiac output increase in response to this physiological stress.25 Shivering movements during neuraxial anesthesia may interfere with monitoring of blood pressure, electrocardiogram, and pulse oximetry,26,27 as well as reducing patient comfort and satisfaction.28
Grading of Shivering Grading and definition of shivering are important to allow meaningful comparisons of interventions in this area. An attempt has been made to grade
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shivering on the following scale: 0, no shivering; 1, piloerection or peripheral vasoconstriction but no visible shivering; 2, muscular activity in only one muscle group; 3, muscular activity in more than one muscle group but not generalized shivering; and 4, shivering involving the whole body.29 An alternative, more user-friendly, scale specific for neuraxial anesthesia would be: 0, no shivering; 1, shivering not interfering with monitoring or causing patient distress; and 2, shivering interfering with patient monitoring or causing patient distress.
Mechanisms Neurophysiology Similar to other physiological systems, the human thermoregulatory system is often divided into 3 components: thermosensors and afferent neural pathways, a center for integration of this input, and effector pathways. Although incompletely understood, many of the neural pathways involved in thermoregulation have been elucidated and summarized elsewhere.30 A simplified schematic representation of the shivering pathway is illustrated in Figure 1. The lateral spinothalamic tract projects to the hypothalamic thermoregulatory centers and to nuclei within the reticular formation in the pons. The nucleus raphe magnus facilitates transmission of thermal information to the hypothalamus and has an inhibitory role in shivering. The locus subcoeruleus appears to have a predominantly excitatory role in shivering. The preoptic area of the anterior hypothalamus appears to be the central integrator of input. The efferent shivering pathway starts at an area between the anterior and posterior hypothalamus and makes
Fig 1. Schematic diagram of the shivering pathway.
multiple connections within the reticular formation before it ends at the ␣ motor neurons. Thermoregulation Undoubtedly, shivering occurs primarily in response to core hypothermia. The normal response to hypothermia involves thermoregulatory vasoconstriction to decrease cutaneous heat loss, and maintain heat within the core. Maximal vasoconstriction usually occurs before thermoregulatory shivering occurs. When the core temperature decreases to a certain point, known as the shivering threshold, thermoregulatory shivering then occurs. The threshold temperature at which shivering occurs may be lower in males relative to females, and may also decrease with age.31,32 A decrease in core temperature (measured at the tympanic membrane) of 0.5°C is sufficient to induce shivering in nonpregnant volunteers undergoing epidural anesthesia.33 The shivering that occurs during epidural anesthesia is accompanied by central hypothermia and peripheral vasoconstriction above the level of the block, and is thus primarily normal thermoregulatory shivering.33 The normal response to warming of the legs is a reduction of the shivering threshold.34 Hynson et al. demonstrated that core hypothermia during the first hour of epidural anesthesia does not result from heat loss to the environment in excess of metabolic heat production, but rather from redistribution of core body heat to the peripheral tissues.35 Matsukawa et al. demonstrated that the magnitude of this decrease for epidural anesthesia was 0.8°C ⫾ 0.3°C in the first hour, and a further 0.4°C ⫾ 0.3°C in the subsequent 2 hours, as well as confirming that redistribution of heat from the core to the periphery is responsible for this decrease.36 Neuraxial block results in impairment of autonomic thermoregulation below the level of the block. The vasodilatation that occurs below the level of a neuraxial block is presumably responsible for this redistribution of heat. One might expect a greater degree of vasodilatation (and thus decrease in core temperature) following spinal block. Saito et al. demonstrated that for the first 30 minutes of anesthesia, core temperature decreased significantly faster in patients given spinal block when compared with those given epidural block. After 30 minutes, core temperatures decreased at identical rates during epidural and spinal anesthesia, with the end result being lower core temperature in the spinal group.13 Thus one might expect higher rates of shivering with spinal block compared with epidural block, but as discussed below, this does not appear to be the case.
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Epidural Versus Spinal Studies comparing the incidence of shivering for epidural versus spinal anesthesia are lacking, although the intensity of shivering seems to be greater during epidural anesthesia.13 Neuraxial anesthesia will block all thermal sensations, but at typical ambient temperatures, is likely to block tonically-firing cold thermoreceptors more than warm thermoreceptors.37 Epidural anesthesia increases the apparent leg temperature (as distinguished from the actual leg temperature) perceived by the body, and this results in a decreased shivering threshold.38 Spinal anesthesia decreases the shivering threshold in direct relation to the number of dermatomes blocked, i.e., less shivering with increased block height.39 To better understand the mechanisms of shivering during neuraxial anesthesia, it is important to try to explain the observed differences between epidural and spinal anesthesia. Spinal anesthesia usually results in complete block of all neurons below a certain level, whereas epidural anesthesia may result in a segmental block that often fails to block sacral dermatomes. Thus, for a given block height, block of thermal input during epidural anesthesia may be reduced relative to spinal anesthesia. This may result in less of a decrease in the shivering threshold relative to spinal anesthesia, and provide a possible explanation as to why shivering appears to be more intense following epidural block. Perhaps the simplest explanation for the apparent difference is the greater intensity of motor block with subarachnoid block compared with that in epidural block, such that patients are actually unable to shiver during subarachnoid block. It is unclear whether epidural or spinal block affect the shivering threshold in different ways. Saito et al., studying 30 parturients having elective cesarean delivery with epidural or spinal anesthesia, demonstrated a higher shivering threshold when using epidural anesthesia.13 In contrast, Ozaki et al., studying 7 male volunteers, failed to show a difference in shivering thresholds for epidural versus spinal anesthesia.40 It is theoretically possible that there are different thermoreceptors and mechanisms within the spinal cord compared with those within the epidural space. Temperature of Administered Fluid It has long been known that the spinal cord has thermoreceptors and is involved in thermoregulation.41 Administration of cold fluids into the epidural space may result in cooling of large epidural veins, which in turn communicate with the basal sinuses. This might also provide an explanation for the apparent difference in shivering intensity for
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epidural and spinal anesthesia. There seems to be some evidence that the temperature of epidural injectate may influence shivering. Ponte et al. found a statistically significant different incidence of shivering when studying 40 patients having elective cesarean delivery and epidural anesthesia. Shivering occurred in 9 of 20 who received epidural bupivacaine at 4°C, compared with 2 of 20 who received epidural bupivacaine at 37°C.42 Shehabi et al. demonstrated a similar reduction in shivering for patients receiving epidural bupivacaine warmed to 36.3°C, compared with bupivacaine at room temperature (22.3°C).6 In a study by Walmsley et al., 30 patients having postpartum tubal ligation received epidural bupivacaine at 4°C, with shivering occurring in 14 of 30 (47%). Eight of the 14 had “marked shivering” and then received further epidural bupivacaine at 41°C, whereupon shivering ceased in 4 of the 8 (50%).43 Two subsequent studies (on volunteers) failed to demonstrate that epidural injectate temperature influences the incidence of shivering, although both studies had small sample size.33,44 It is unknown whether or not the temperature of intrathecal injectate influences shivering. The temperature of intravenous fluids may also contribute to shivering. Workhoven et al., studying 44 parturients having elective cesarean delivery and epidural anesthesia, demonstrated that shivering occurred in 14 of 22 who received room temperature (20°C22.2°C) intravenous crystalloid. This compared with only 3 of 22 who received warmed (30°C33.9°C) intravenous fluids.3 General Versus Neuraxial Although the pathophysiological mechanisms of shivering during general anesthesia and neuraxial anesthesia are intertwined, there are subtle differences. For both, significant vasodilatation that results in heat loss may result in thermoregulatory shivering. During general anesthesia, normal thermoregulatory mechanisms are impaired by incompletely understood mechanisms, and thus shivering usually occurs only on awakening. Segmental block of neural input during neuraxial anesthesia constitutes a unique causative mechanism and also allows a degree of compensatory vasoconstriction and shivering above the level of the block. General and neuraxial anesthesia have distinct effects on the release of stress hormones, metabolic heat production, and transmission along pain pathways; all of which may have differing effects on thermoregulation and shivering. Electromyographic studies of shivering, using isoflurane anesthesia in volunteers (not undergoing surgery), revealed that shivering is composed of 2 distinct patterns of muscular activity: a
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tonic pattern with 4 to 10 cycles per minute, resembling normal thermoregulatory shivering, and a clonic pattern of 5 to 7 cycles per second, consistent with uninhibited spinal reflexes.45 It was also demonstrated that deep tendon reflexes are significantly exaggerated by central hypothermia. Analysis of electromyographic patterns of shivering, following epidural anesthesia in nonpregnant volunteers, revealed the tonic pattern of normal thermoregulatory shivering but failed to demonstrate any clonic tremor pattern.35 Pregnancy Many of the studies on shivering feature parturients having labor epidural analgesia or cesarean delivery with epidural or spinal anesthesia. Although there are no studies comparing shivering in this group versus males or nonpregnant females, the median incidence in published studies for this group is 52.5% (interquartile range of 36%-71%).2,4,6-8,10,11,13,14,17,18,21 This occurs despite the increase in temperature that normally occurs during labor,46 and the increase in temperature associated with epidural analgesia.47,48 A review of the hyperthermia related to labor epidural analgesia (and the associated shivering) offered many theories as to its causation, but it remains something of an anomaly.49 Indeed it is possible that shivering during labor (with or without neuraxial anesthesia) may be a phenomenon different than thermoregulatory shivering in a non-pregnant population. Shivering that occurs in the context of hyperpyrexia will lead to a further increase in temperature. It is known that the shivering threshold varies with gender, with females shivering at a higher threshold temperature relative to males.31 The influence of hormonal changes during pregnancy on shivering is unknown. Thermoregulatory shivering may occur in up to 14.5% of laboring women even before epidural block.2 Shivering during epidural block is more common among parturients who shiver prior to institution of epidural block, and in those who receive nitrous oxide.2 It has long been hypothesized that the shivering that occurs in the peripartum period may be an immunological result of fetomaternal transfusion.50,51 Nonthermoregulatory shivering also occurs in parturients with labor epidural analgesia.52 Opioids Opioid peptides have varying effects on body temperature.53 Intrathecal and epidural opioids commonly cause a small decrease in core temperature.54-56 One might expect increased shivering to occur as a result. However as discussed below, ad-
ministration of opioids plays a significant role in the prevention and treatment of shivering.
Prevention and Treatment Nonpharmacological Measures The redistribution of heat from the core to peripheral tissues, which occurs during neuraxial anesthesia, may cause hypothermia, which in turn may result in thermoregulatory shivering. By warming the peripheries, it should be possible to reduce this temperature gradient, and thus reduce shivering. Glosten et al. prewarmed volunteers for 2 hours, using a forced-air warming mattress set to 38°C, before performing epidural block. They demonstrated significantly higher skin temperatures, smaller decrease in core temperature, and reduced incidence of shivering, when compared with unwarmed volunteers.57 Horn et al. prewarmed parturients, who were having elective cesarean delivery with epidural anesthesia, for 15 minutes using a forced-air warming cover set to 43°C, and demonstrated significantly higher core temperatures, and less shivering in the prewarmed group. Interestingly, they also demonstrated that babies of prewarmed mothers had significantly higher rectal temperatures (37.1°C ⫾ 0.5°C vs. 36.2°C ⫾ 0.6°C), and umbilical vein pH (7.32 ⫾ 0.07 vs. 7.24 ⫾ 0.07).14 In contrast, application of an intraoperative forced-air warmer to the lower body of parturients having elective cesarean delivery and spinal anesthesia did not prevent intraoperative hypothermia or shivering.21 In this study, shivering was not the primary outcome, and thus the sample size may have been inadequate to demonstrate a difference. The application of a forced-air warmer to those with established shivering following general anesthesia was also not beneficial.58 Using an aluminum space blanket, in parturients having labor epidural analgesia, Buggy and Gardiner reduced the intensity of shivering, but failed to increase skin temperature, and thus failed to reduce the incidence of shivering.10 Wrapping of the legs in elastic bandages did not decrease the incidence of shivering in parturients having cesarean delivery with epidural anesthesia.17 Pharmacological Measures Much work has been done to examine the effects of multiple pharmacological agents on thermoregulation and shivering. Many of the studied agents have analgesic and sedative properties, and probably influence thermoregulation via effects on neurotransmission and neuronal receptors. Agents usually mediate effects via one or more of the
Table 1. Pharmacological Agents Used in the Prevention and Treatment of Neuraxial Anesthesia Shivering Agent (Pharmacology)
Dose
Route
Study Population
Number of Subjects
Time of Administration
32 Treatment; 48 control
Epidural initiation
Significantly decreased
None
Labor epidural analgesia
32 Treatment; 29 control
Established shivering
Significantly decreased
None
Juneja60
Male, urological surgery, spinal anesthesia Knee arthroscopy, spinal anesthesia Labor epidural analgesia and epidural for cesarean delivery Extracorporeal shock lithotripsy, epidural anesthesia Labor epidural analgesia
48 Treatment; 52 control
90 Minutes before spinal
Significantly decreased
Not mentioned
Mao61
50 Treatment; 50 control
Spinal initiation
Significantly decreased
None
Sia12
20 Treatment; 20 control
Established shivering
Decreased; significance unknown
Hypotension with 90 mcg
20 Treatment; 20 control
20 Minutes before epidural
Significantly decreased
Drowsiness
Yang9
20 Treatment; 20 control
Established shivering post delivery
Significantly decreased
Mercadante63*
50 Treatment; 50 control
5 Minutes before spinal
Significantly decreased
Decreased heart rate and blood pressure; increased drowsiness Sedation
50 Treatment; 50 control
Spinal initiation
No change
None
Jeon19†
31 Treatment; 38 control
Established working epidural
Significantly decreased
Increased sedation
Buprenorphine (mixed ,␦, and opioid agonist/antagonist) 0.3 mg Epidural Labor epidural analgesia
Butorphanol ( agonist and competitive antagonist) 1 mg Epidural Clonidine (␣2 agonist) 150 mcg
Oral
Intravenous
150 mcg
Intravenous
150 mcg
Intravenous
1 mcg/kg
Intravenous
150 mcg
Intrathecal
4.5 mcg/mL (median dose 28 mcg/hour)
Patient-controlled epidural analgesia
Orthopedic surgery, spinal anesthesia Orthopedic surgery, spinal anesthesia Labor epidural analgesia
German language; unknown sample size calculation.
75% success with 30 mcg; crossover design.
Report First Author
Lehmann59
Capogna62
Jeon19†
Shivering not primary outcome measure.
Paech64
Crowley and Buggy
30 mcg bolus every 5 minutes to maximum of 90 mcg
Notes
•
Intravenous
Side Effects
Shivering and Neuraxial Anesthesia
1 mcg/kg
Incidence of Shivering
245
246
Agent (Pharmacology)
Dose
Route
Study Population
Number of Subjects
Time of Administration
Incidence of Shivering
Side Effects
Notes
Report First Author
Fentanyl ( agonist) 25 mcg
Epidural
50 mcg
Epidural
25 mcg
Epidural
100 mcg bolus and 50 mcg/ hour infusion
Epidural
20 mcg
Intrathecal
Elective cesarean delivery, spinal anesthesia
Intravenous
Urological surgery, spinal anesthesia
Granisetron (5-HT3 antagonist) 3 mg
Labor epidural analgesia and epidural for cesarean delivery Labor epidural analgesia Elective cesarean delivery, epidural anesthesia Male, extracorporeal shockwave lithotripsy, epidural anesthesia
Established shivering
Significantly decreased
Nausea/vomiting
21 Treatment; 20 control 18 Treatment; 23 control
Epidural initiation
Significantly decreased Significantly decreased
Not mentioned Nonsignificant increase in nausea/vomiting
Papavertum, metoclopramide for some patients.
Liu8
Total of 14 patients, number in each group not recorded; no control 30 Treatment; 30 control
Epidural initiation
Shivering threshold significantly decreased in fentanyl group
Not mentioned
Significantly more intravenous fluid in fentanyl group.
Wheelahan66
At spinal initiation
Statistically significant decrease
Not significant
40 Treatment; 40 control
At spinal initiation
Decreased but significance not analyzed
Hypotension in 8, and nausea and vomiting in 1, of 40 subjects in treatment group; significance unknown
Baseline axillary and core temperature significantly different among groups; metoclopramide given to some patients.
Sagir20‡
At spinal initiation
Statistically significant decrease
Hypotension in 3 of 40 subjects in ketamine group
Group of ketamine 0.25 mg/kg with granisetron 1.5 mg also decreased shivering but significance not analyzed.
Sagir20‡
Ketamine (NMDA agonist, stimulates sympathetic nervous system, ␦ and agonist, antagonist) 0.5 mg/kg Intravenous Urological 40 Treatment; surgery, 40 control spinal anesthesia
Epidural initiation
Heterogeneous group; some patients shivering before epidural; use of nitrous oxide.
Matthews65
20 Treatment; 21 control
Shehabi6
Techanivate67
Regional Anesthesia and Pain Medicine Vol. 33 No. 3 May–June 2008
Table 1. (Continued)
Table 1. (Continued) Agent (Pharmacology)
Dose
Route
Study Population
Number of Subjects
Time of Administration
Meperidine ( and ␣2 agonist, NMDA antagonist, inhibits 5-HT and norepinephrine uptake, antimuscarinic) 25 mg Epidural Labor epidural 11 Treatment; Established analgesia 11 control shivering
Elective cesarean delivery, epidural anesthesia Extracorporeal shockwave lithotripsy, epidural anesthesia
Intravenous
50 mg
Intravenous
Labor epidural analgesia
50 mg
Intravenous
0.5 mg/kg
Intravenous
Cesarean delivery, epidural anesthesia Cesarean delivery, epidural anesthesia
0.4 mg/kg
Intravenous
10 mg
Intrathecal
0.2 mg/kg
Intrathecal
Elective orthopedic surgery, spinal anesthesia Elective cesarean delivery, combined spinalepidural Nonemergent cesarean delivery, spinal anesthesia
Not significant
Nitrous oxide and intramuscular meperidine also used.
Report First Author
Brownridge2
47 Treatment; 47 control
Epidural initiation
Significantly decreased
Not significant
Sutherland7
19 Treatment (12.5 mg) and 21 treatment (25 mg); 20 control 20 Treatment; 20 control
15 to 30 minutes before epidural initiation
Nonsignificant trend to decrease for both doses
Not mentioned
Harris5
Established shivering post delivery
Significantly decreased
Mercadante63*
20 Treatment; 20 control
Established shivering
Significantly decreased
Decreased heart rate and increased drowsiness Increased drowsiness
15 Treatment, other treatment groups of amitriptyline and tramadol; no control 25 Treatment; 25 control
Established shivering
Significantly decreased compared with amitriptyline group
Increased somnolence
Tsai68§
At spinal initiation
Significantly decreased
None
Kelsaka69储
30 Treatment; 30 control
At spinal initiation
Significantly decreased
Not significant
20 Treatment; 20 control
At spinal initiation
Significantly decreased
Not significant
Casey4
Intravenous diphenhydramine and metoclopramide to some patients.
Hong70
Roy18
Crowley and Buggy
12.5 or 25 mg
Significantly decreased
Notes
•
Epidural
Side Effects
Shivering and Neuraxial Anesthesia
25 mg
Incidence of Shivering
247
248
Agent (Pharmacology)
Dose 25 mg
Route
Lower abdominal/ extremity surgery, spinal anesthesia Nefopam (inhibits uptake of 5-HT, norepinephrine, and dopamine) 0.15 mg/kg Intravenous Orthopedic surgery, epidural or spinal anesthesia Neostigmine (anticholinesterase) 75, 150, or Epidural Elective 300 mcg cesarean delivery, combined spinalepidural anesthesia Ondansetron (5-HT3 antagonist) 8 mg Intravenous Elective orthopedic surgery, spinal anesthesia
Sufentanil ( agonist) 0, 25, 50, 75, or 100 mcg
Intramuscular
Study Population
Epidural
Number of Subjects
Time of Administration
Incidence of Shivering
Side Effects
Notes
Report First Author
30 Treatment; 30 control
15 Minutes before spinal
Significantly decreased
Not mentioned
Chinese language.
Hu71
30 Treatment; 30 control
At induction of anesthesia
Significantly decreased
Nausea, vomiting, sweating; unknown significance
Nefopam significantly better than tramadol.
Bilotta16¶
20 Treatment for each dose; 20 control
Post cord clamping
Significantly increased with 300 mcg
Increased sedation
Unknown incidence of shivering at cord clamping; shivering not primary outcome.
Kaya72
25 Treatment; 25 control
At spinal initiation
Significantly decreased
Statistically significant bradycardia
Similar effectiveness for meperidine 0.4 mg/kg and ondansetron 8 mg, but not an equivalence study.
Kelsaka69储
Established shivering
Decreased when dose ⬎50 mcg; significance unknown
Not mentioned
0.2 mcg epidural epinephrine given to some patients.
Burks53
Established shivering
Significant decrease in time to stop shivering Significantly decreased
Increased nausea/ vomiting
Japanese language.
Chen73
Not significant
No difference in response rate or side effects for both doses.
Chan74
Elective 40 Treatment; repeat No control cesarean delivery, epidural anesthesia Tramadol (opioid agonist, inhibits reuptake of 5-HT, norepinephrine, and dopamine) 1 mg/kg Intravenous Nonparturients, 30 Treatment; epidural 30 control anesthesia 0.25 mg/kg Intravenous Elective or 13 Treatment or 0.5 mg/kg emergency (0.25 mg/ cesarean kg) and 12 delivery, treatment epidural (0.5 mg/ anesthesia kg); 11 control
Established shivering
Regional Anesthesia and Pain Medicine Vol. 33 No. 3 May–June 2008
Table 1. (Continued)
Tsai68§
Bilotta16¶
Not significant
Nausea, vomiting, sweating; unknown significance Significantly decreased At induction of anesthesia
Significantly decreased compared with amitriptyline group Established shivering
*Same study. †Same study. ‡Same study. §Same study. 储Same study. ¶Same study.
Male and female, orthopedic surgery, epidural or spinal anesthesia Intravenous 0.5 mg/kg
Crowley and Buggy
249
Future Directions
15 Treatment, other treatment groups of amitriptyline and meperidine; no control 30 Treatment; 30 control Intravenous 0.5 mg/kg
Cesarean delivery, epidural anesthesia
Side Effects Incidence of Shivering Time of Administration Number of Subjects Study Population Route Dose Agent (Pharmacology)
Table 1. (Continued)
•
cholinergic, cationic, endogenous peptide, monoamine, N-methyl-D-aspartate, and serotonergic systems. Thermomodulation may occur, at peripheral receptors, at spinal cord level, or centrally, with some agents undoubtedly acting at multiple sites and at multiple receptors. Agents may also demonstrate differing effects depending on the route of administration. This complexity is reflected by the multitude of agents whose effects on thermoregulation and shivering following general anesthesia have been studied.30 Table 1 details studies on pharmacological agents whose effects on the shivering specific to neuraxial anesthesia have been examined.
Notes
Report First Author
Shivering and Neuraxial Anesthesia
The exact mechanisms underlying the observed differences in the intensity of shivering for epidural anesthesia and spinal anesthesia remain incompletely understood. It is also unclear whether or not epidural and spinal block affect thermoregulation to the same extent for a similar block height. Parturients may represent a special group, and the effects (if any) of thermomodulation on the fetus are unknown. It is unknown whether the choice of local anesthetic compound affects the incidence of shivering, although it has been speculated that shivering may occur more frequently when bupivacaine is used for epidural anesthesia.75 The shivering that occurs during general anesthesia and neuraxial anesthesia share some common pathways. Thus, it seems likely that agents that have proven successful in the treatment of shivering following general anesthesia, e.g., doxapram,76 ketanserin,77 physostigmine,78 and propofol,79 might also be useful in the management of shivering during neuraxial anesthesia. Any agent that interacts with neurotransmission, in particular via the dopaminergic and serotonergic pathways, is likely to have effects on thermoregulation, and possibly on shivering. A possible role exists for vasoconstrictor agents, which may reduce the loss of heat from the core to peripheral tissues. Exogenous intravenously administered prostaglandin E1 has been shown to reduce peripheral blood flow, temperature, and shivering.80 This raises questions about the potential effects of nonsteroidal anti-inflammatory drugs on thermoregulation. The intravenous administration of amino acid mixtures prevents the hypothermia that occurs during spinal anesthesia, which may have positive affects on blood loss and the incidence of shivering.81,82 As Table 1 demonstrates, many pharmacological agents reduce the incidence of shivering. However, it still remains unclear which agents may be most effective with the lowest inci-
250
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Table 2. Suggested Strategies to Prevent and Treat Neuraxial Anesthesia Shivering Prevention Pre-warm patient with a forced air warmer for at least 15 minutes.14 Avoid administration of cold epidural and intravenous fluids.3,6,42,43 Intrathecal fentanyl 20 mcg.67 Intrathecal meperidine 0.2 mg/kg or 10 mg.18,70 Intravenous ondansetron 8 mg.69 Epidural fentanyl 25 mg or 50 mg.6,8 Epidural meperidine 25 mg.7 Treatment Intravenous meperidine 50 mg.4,63 Intravenous tramadol 0.25 mg/kg or 0.5 mg/kg or 1 mg/kg.73,74 Intravenous clonidine 30, 60, 90 or 150 mcg.62,63
dence of side effects. We require further good quality, prospective, randomized trials of adequate sample size, comparing the effects of an intervention versus control on neuraxial shivering, where this shivering is defined or graded, and, is the primary outcome measure.
Conclusion Shivering that occurs due to neuraxial anesthesia is relatively common, and incompletely understood (particularly in the parturient). It is likely that any factor that causes core hypothermia may result in thermoregulatory shivering. The shivering threshold may also be altered by many factors, e.g., the level and type of block, and a multitude of pharmacological agents. The interplay between these known and unknown factors determines whether shivering occurs. As this review has demonstrated, there are effective pharmacological and nonpharmacological mechanisms to reduce the incidence of this shivering. Unfortunately, the heterogeneity of study populations and design make it difficult to apply strict evidence-based principles to the problem. Table 2 provides a suggested strategy for the prevention and treatment of neuraxial shivering, based on the authors’ opinions regarding ease of application, the number and quality of published studies, and the likelihood of side effects. We must always remember that shivering is usually a normal thermoregulatory response to a potentially harmful decrease in core temperature. Thus, if we apply mechanisms to reduce this shivering, we must ensure that we are adequately monitoring patient temperature and supplying adequate heat to our patients.
Acknowledgments The authors thank Drs. Joanne Douglas and Roanne Preston for advice and guidance.
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