Authors
- Hoffman, Jeffrey RRNA, RN, BSN
- Hamner, Casi RRNA, RN, BSN
Abstract
Review question/objective: The following question guides the systematic review: In adult patients undergoing general anesthesia, what is the effectiveness of dexmedetomidine, compared to placebo, in preventing shivering in the first two hours after surgery?
The objective of this systematic review is to synthesize the best available evidence on the efficacy of dexmedetomidine in preventing the occurrence of postanesthetic shivering (PAS).
Background: Shivering is a common phenomenon noted after surgery and occurs in up to 66% of patients who received general anesthesia.1-6 Postanesthetic shivering can be uncomfortable to the patient leading to increased pain at the surgical site.6 Shivering can increase metabolic demand up to 600% leading to hypoxemia, elevated carbon dioxide production, lactic acidosis and increased circulating catecholamine levels.2,7,8,9 These side effects place patients with cardiac and pulmonary impairment at an increased risk of adverse outcomes.9 Other adverse effects of shivering include increased intracranial and intraocular pressures, tachycardia, and hypertension.2,8 Shivering can also interfere with the accuracy of postanesthesia monitoring of blood pressure, heart rate, pulse oximetry and electrocardiogram.8,10,11 The prevention and treatment of shivering can help decrease the postoperative complications as listed above and aid in a smoother recovery from general anesthesia.12
Perioperative hypothermia occurs in three phases during general anesthesia: first, a rapid redistribution of body heat to the periphery resulting in a 1-2[degrees]C decrease in temperature due to anesthetic-induced vasodilation; second, a slower, more gradual decrease in core temperature over the next two to four hours; finally, a lower steady-state temperature is reached with a slowed rate of heat loss noted.9,13 Risk factors for perioperative hypothermia include extremes of age, type and length of surgical intervention, environmental factors (radiation, convection, conduction, and evaporation), anesthetic agents and other perioperative medications.12
Shivering, vasoconstriction and nonshivering thermogenesis are the body's way to compensate for heat loss and restore homeostasis.2,8,14 Shivering is characterized by involuntary muscle contractions and vasoconstriction in an attempt to increase metabolic activity and heat production. 4 General anesthetics inhibit the thermoregulation center of the hypothalamus by lowering the shivering threshold and preventing the compensatory mechanism of shivering. The use of muscle relaxants will also inhibit the body's ability to shiver.2 Once anesthetic medications are discontinued, the compensatory mechanisms are restored, increasing the likelihood of the body to shiver. Postanesthetic shivering also occurs in the normothermic patient, which has led to researching pharmacologic prophylaxis and treatment options for shivering.3,7,12 As listed above, the consequences of shivering can be detrimental to patient outcomes, exemplifying the importance of preventive measures with forced air warmers, warmed fluids, humidified ventilators and medications.4,7
Numerous agents have been identified as having antishivering properties.11,15 Studies have found nefopam, tramadol, physostigmine, meperidine (pethidine), clonidine, morphine, fentanyl, doxapram, ketamine, nalbuphine, and ketanserin as effective agents for use in preventing PAS. 11,15,16 Although many medications have been examined in the literature, no single medication has been identified as the gold standard for pharmacologic prophylaxis or management of PAS.15,17 Despite its adverse side effects, meperidine is often considered the best agent for PAS and is the most common medication used in treating it.9,16,17,18 Recent practice guidelines for postanesthetic care by the American Society of Anesthesiologists states no other opioid agonist or agonist-antagonist has been found to be more effective than meperidine at treating PAS.18 Reported adverse effects of meperidine include nausea and vomiting, significant drowsiness, dizziness and respiratory depression.16 Common side effects of other PAS prophylaxis medications also include nausea, vomiting and respiratory depression along with hypotension, drowsiness and pruritus. 16 These side effects increase the potential for patient discomfort and physiologic decompensation.
Recent studies have examined the use of intraoperative dexmedetomidine as a method of decreasing PAS. Dexmedetomidine is a highly selective [alpha] 2-adrenoceptor agonist that causes sedation, analgesia, anxiolysis and attenuation of the neuroendocrine and hemodynamic responses to anesthesia and surgery.19 It has also been found to decrease the vasoconstriction and shivering thresholds; making dexmedetomidine a plausible modality in the prevention of PAS.20 The exact role of the [alpha]2 receptor in PAS has yet to be completely identified. [alpha]2 receptors are located on blood vessels and sympathetic terminals and within the central nervous system and spinal cord.21 Deexmedetomidine's effect on PAS is thought to be through centrally mediated actions.14 Dexmedetomidine's [alpha]2-/[alpha]1-adrenoreceptor selectivity is 1,620:1, compared to clonidine's 220:1.22 This degree of [alpha]2 selectivity provides dexmedetomidine with a more desirable pharmacokinetic profile.22 Bolus dosing of 1 [mu]g/kg dexmedetomidine, a common administration technique, has been associated with transient increases in blood pressure associated with a reflex decrease in heart rate.21 These negative effects can be attenuated by slowing infusion rates or decreasing bolus doses. Doses as low as 0.75 [mu]g/kg, infused over 10 minutes, have been shown to be effective at preventing PAS when administered 30 minutes prior to the end of surgery.7 Intraoperative administration of dexmedetomidine, both single bolus doses of 0.75-1 [mu]g/kg infused over 10 minutes and bolus doses of 1 [mu]g/kg followed by an infusion of 0.4 [mu]g/kg/hr, administered at various times during the surgical procedure have been associated with an increased need for atropine, delayed extubation and increased sedation.7,12,23 However, no major impact on overall recovery from anesthesia has been noted and dexmedetomidine continues to be explored as a possible PAS prophylactic agent. 7,12,23
The Joanna Briggs Institute (JBI), Cochrane Library of Systematic Reviews, EMBASE, PubMed, and PROSPERO databases were searched prior to conducting this review. A similar review was initiated on September 25, 2014 in PROSPERO, but the protocol does not define the specific type of anesthesia as outlined in this review. A meta-analysis was published in 2013 evaluating the efficacy of dexmedetomidine as an anesthetic adjunct in surgery. This analysis did not focus on the treatment or prevention of PAS but the results did support that perioperative dexmedetomidine reduced the incidence of PAS.24 This systematic review is needed to evaluate the effectiveness of dexmedetomidine for the prevention of PAS.
Definition of terms used in this review:
Postoperative shivering or post-anesthetic shivering (PAS) is an involuntary, tremor-like, defense mechanism to increase the body's heat production following general anesthesia.4 PAS was monitored by direct observation and recorded by a yes/no response or variation of a 4 or 5 point Likert shivering scale.
General anesthesia is the reversible drug induced depression of perception, consciousness and awareness of one's external environment.25
Normothermia (normothermic) is defined as a body temperature within the range of 36.5-37.5[degrees]C and hypothermia is any temperature less than 36.5[degrees]C. 8
Thermoregulation (thermogenesis) is the body's compensatory mechanism to maintain a normothermic temperature based on physiological changes sensed by central and peripheral thermal receptors.8 Thermoregulatory effects that maintain a normal body temperature include vasoconstriction, vasodilation, shivering, and sweating.4
Article Content
Inclusion Criteria
Types of participants
This review will consider studies that include adult patients between 18 and 70 years of age receiving general anesthesia for any surgical procedure in any clinical setting. Only studies examining patients with American Society of Anesthesiologist physical status 1 or 2 will be considered. Studies including anesthetic techniques other than general anesthesia will be excluded. Studies including patients less than 18 years of age will also be excluded, as the incidence of PAS in this population is low and the risk to benefit ratio doesn't warrant prophylactic treatment.26,27
Type of intervention
This review will evaluate the effectiveness of dexmedetomidine in preventing PAS. Studies that compare preoperative or intraoperative administration of dexmedetomidine to placebo will be considered. Only intravenous administration techniques of dexmedetomidine will be included. Studies to be examined will include dexmedetomidine administration times of 30 minutes prior to induction of general anesthesia and any other intraoperative administration times. Dexmedetomidine boluses and infusions will be completed prior to patient arrival to post-anesthesia care unit (PACU). Studies will be excluded if the dexmedetomidine is administered during PACU stay. Examined studies will include the administration of dexmedetomidine as a one-time bolus, continuous infusion, or a combination of bolus and infusion doses. Only studies evaluating dexmedetomidine as the sole pharmacological agent in the prevention of PAS will be considered. Studies evaluating dexmedetomidine for the treatment of PAS will be excluded.
Types of outcomes
This review will consider studies that include the following outcome measure: presence of PAS observed in the PACU during the first hour after the completion of surgery. Intensity of shivering will be measured with variations of a shivering scale validated by Crossley and Mahajan as follows: 0 = no shivering, 1 = mild fasciculation of the face or neck, 2 = visible tremor involving more than one muscle group, 3 = gross muscular activity involving the entire body.28
Types of studies
This review will include all experimental and epidemiological study designs including randomized controlled trials (RCTs), non-randomized controlled trials, quasi-experimental, before and after studies, prospective and retrospective cohort studies, case control studies and analytical cross sectional studies.
Search strategy
The search strategy aims to find both published and unpublished studies. A three-step search strategy will be utilized in this review. An initial limited search of PubMed and CINAHL will be undertaken followed by analysis of the text words contained in the title and abstract, and of the index terms used to describe articles. A second search using all identified keywords and index terms will then be undertaken across all included databases. Thirdly, the reference list of all identified reports and articles will be searched for additional studies. Only studies published in English or available in English translation will be considered for inclusion in this review. Studies published between 1999 and 2014 will be considered for inclusion in this review. Inclusion dates indicate when dexmedetomidine was first approved in the US; other countries around the world approved its use after the US.
Databases to be searched include:
CINAHL, Clinical Key, EMBASE, ProQuest Nursing, PubMed, Science Direct, Cochrane and Web of Science.
The search for unpublished studies will include:
Google Scholar and ClinicalTrials.gov.
Initial keywords to be used:
Dexmedetomidine OR precedex, shiver OR shivering, anesthesia OR anaesthesia, postoperative OR postanesthetic
Assessment of methodological quality
Quantitative papers selected for retrieval will be assessed by two independent reviewers for methodological validity prior to inclusion in the review using standardized critical appraisal instruments from the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) (Appendix I). Any disagreements that arise between the reviewers will be resolved through discussion or with a third reviewer.
Data collection
Data will be extracted from papers included in the review using the standardized data extraction tool from JBI-MAStARI (Appendix II). The data extracted will include specific details about the interventions, populations, study methods and outcomes of significance to the review question and specific objectives.
Data synthesis
Quantitative data will, where possible, be pooled in statistical meta-analysis using JBI-MAStARI. All results will be subject to double data entry. Effect sizes expressed as odds ratio (for categorical data) and weighted mean differences (for continuous data) and their 95% confidence intervals will be calculated for analysis. Heterogeneity will be assessed statistically using the standard Chi-square and also explored using subgroup analyses, such as study quality, intervention difference, population differences and outright exclusions. Where statistical pooling is not possible the findings will be presented in narrative form.
Conflicts of Interest
There are no conflicts of interest to report. There is no external funding for this review.
Acknowledgements
This systematic review will contribute to the reviewers Doctor of Nursing Practice-Anesthesia (DNP-A) at Texas Christian University in Fort Worth, Texas.
References
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Appendix I: Appraisal Instruments
MAStARI appraisal instruments[Context Link]
Appendix II: Data Extraction Instruments
MAStARI data extraction instrument[Context Link]
Keywords: Dexmedetomidine; shiver; shivering; anesthesia; anaesthesia; postoperative; postanesthetic