Background

Many patients undergoing surgical procedures have multiple coexisting medical conditions, which could increase the risk of intraoperative and postoperative complications. Spinal anesthesia is an alternative to general anesthesia and provides an adequate blockade for many types of surgical procedures. Spinal blockades serve to blunt autonomic, somatic and endocrine responses and result in tolerable pain management to expedite recovery.1 The sensory blockades interrupt the transmission of painful stimuli, thus blocking both somatic and visceral pain.2 Spinal anesthesia has proven to be useful as the primary anesthetic for lower abdominal, inguinal, urogenital, rectal and lower extremity surgery.2 There are many advantages to using a spinal anesthetic technique, including analgesia, minimal side effects and a shorter post-anesthesia care unit stay.3 Spinal anesthesia has also shown to reduce morbidity and mortality rates and decrease the incidence of complications when compared to general anesthesia.2 A potential, undesirable effect of spinal anesthesia, which may outweigh the advantages and limit its use, is the short duration of action, often requiring early analgesic interventions to manage pain postoperatively.4 However, studies have found that dexmedetomidine, a newer and more selective alpha 2 adrenergic agonist, is a useful adjuvant to prolong local anesthetics for spinal anesthesia.1,4-11

The primary site of action of spinal anesthesia is thought to be the nerve root.2 Through direct injection of local anesthetic into the cerebral spinal fluid, the nerve root is bathed in local anesthetic.2 This results in the interruption of afferent and efferent transmission at the nerve fibers, allowing spinal anesthesia to achieve sympathetic, sensory and motor blockades.2 It is important to note that nerve fibers serve different functions, which has an effect on their sensitivity to the local anesthetic and this, in turn, manifests as a differential nerve block.12 Differential blockade results in the sympathetic block to occur first, followed in order by sensory and motor blocks.12 The differential blockade also results in the sympathetic block being two to six dermatomes higher than the sensory block, which, in turn, is usually two to three dermatomes higher than the motor block.12 The sensory dermatome level, which is a measurement of the skin area innervated by a particular spinal nerve and corresponding cord segment, is used to assess the height of the block at initial spinal injection and to monitor the level of the block at frequent time intervals.12 Spinal anesthesia does not resolve abruptly, but the block level gradually regresses over time. The duration of the sensory blockade is determined based on time measurements of two-dermatome regression and complete block resolution.8 Bupivacaine, a commonly used local anesthetic for spinal anesthesia, maintains a sensory block for approximately 90-140 minutes until two-dermatome regression, with complete resolution ranging from 240 to 380 minutes.12 The duration and quality of the spinal blockade is crucial for maintaining adequate analgesia and anesthesia throughout the surgical procedure.

To improve analgesic and anesthetic quality, adjuvants are often combined with local anesthetics for spinal anesthesia. Intrathecal opioids are frequently used as adjuvants; however, there are many undesirable side effects associated with opioid use, including: urinary retention, pruritus, nausea and vomiting and respiratory depression.13 Dexmedetomidine, a highly selective alpha 2 adrenergic agonist, is an intravenous sedative that works for both the brain and the spinal cord.5 This newer drug has been investigated for off-label use as a co-analgesic drug due to its antinociceptive or pain inhibiting effects that block both somatic and visceral type pain.4 Dexmedetomidine produces its analgesic effect by blocking the release of C-fiber transmitters at the level of the spinal cord, making it a useful adjuvant for spinal anesthesia.6 Dexmedetomidine produces dose-dependent anxiolytic, analgesic and sedative effects and also plays a role in blunting the sympathetic nervous system response to surgery.2 Dexmedetomidine has an opioid-sparing effect and provides analgesia without the associated potential for respiratory depression and airway obstruction.6 In addition, the decreased use of opioids reduces the risk of atelectasis, respiratory depression causing hypoventilation, aspiration pneumonia and postoperative ileus.2

Dexmedetomidine has been found to have a synergistic action with local anesthetics used for spinal anesthesia. Studies have found that the use of dexmedetomidine combined with local anesthetics prolongs the sensory blockade's duration in comparison to local anesthetics alone, aiding in reduced sensitivity to pain and prolonged analgesia.3 The combination of these actions make dexmedetomidine a potent antinociceptive agent that provides quality intraoperative and postoperative analgesia with minimal side effects.5 Effective intraoperative and postoperative pain management is an important component in reducing perioperative morbidity and promoting early postoperative recovery.13 These characteristics make dexmedetomidine an attractive choice for spinal anesthesia in patients requiring surgical procedures. Studies show that the use of spinal dexmedetomidine may be beneficial to improve the quality of spinal anesthesia, potentiate the analgesic efficacy, provide prolonged postoperative analgesia and lower postoperative pain scores.6

A preliminary search of the Cochrane Library, the JBI Database of Systematic Reviews and Implementation Reports and the PROSPERO database was undertaken. The search found one systematic review published in 2014 by Wu et al.14 which examined the neuraxial application of dexmedetomidine as an adjuvant analgesic to ropivicaine and bupivacaine in both adult and pediatric patients. Sixteen randomized control trials involving 1092 participants were included and showed that the use of neuraxial dexmedetomidine significantly decreased postoperative pain intensity, lengthened the duration of the analgesic, but also increased bradycardia risk in patients. The current systematic review will review dexmedetomidine as an adjuvant to bupivacaine and will only include adult patients undergoing elective surgery. Emergency and trauma surgeries will not be included in this review due to the unusual challenges of such conditions. Trauma anesthesia creates complexities relating to mechanism of action, multisystem injury and urgency of surgical intervention that may interfere with routine preoperative evaluation and perioperative management.12

Inclusion criteria

Types of participants

The current review will consider studies that include adult surgical patients aged 18-75 years old, with an American Society of Anesthesiologists (ASA) classification of I, II or III, undergoing elective surgery and who received intrathecal dexmedetomidine as an adjuvant to bupivacaine spinal anesthesia. The ASA physical status classification is a preoperative assessment used to determine the patient's anesthetic risk based on the patient's overall health.9 The ASA score is based on five classes: (I) completely healthy fit patient, (II) patient has mild systemic disease, (III) patient has severe systemic disease that is not incapacitating, (IV) patient has incapacitating disease that is a constant threat to life and (V) patient who is not expected to live 24 hours with or without surgery.9

Adult patients receiving general anesthesia, as well as, adult patients with neuromuscular diseases, diabetes mellitus or have a history of opioid dependency, tolerance or opioid-induced hyperalgesia will be excluded. Neuromuscular diseases are associated with generalized muscle weakness, unpredictable and widely variable response to drugs and reduced margin of safety of anesthetic agents.12 Long-term diabetes-mellitus-related complications, on the other hand, include sensory and motor neuropathy and autonomic nervous system dysfunction.12 Chronic opioid therapy places the patient at risk for higher postoperative pain levels and slower pain resolution than normal.12

Types of intervention

The current review will consider studies that evaluate the effects of using intrathecal dexmedetomidine as an adjuvant to bupivacaine spinal anesthesia in patients undergoing elective surgical procedures.

Types of comparator

The intervention will be compared to the sole use of bupivacaine spinal anesthesia.

Outcomes

The current review will consider studies that include the following outcome measures: assessment of pain as exhibited by single-dimension pain scales or postoperative analgesia duration (time to first analgesic requirement). Examples of single-dimension pain scales include the Visual Analog Scale, Numeric Rating Scale or Wong-Baker FACES Pain Rating Scale.

Types of studies

Randomized controlled trials will be considered for inclusion in the review.

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 MEDLINE (Ovid) 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 the article. A second search using all identified keywords and index terms will then be undertaken across all included databases. Third, 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. If appropriate, for articles located in other languages, authors will be contacted to identify if they are also published in English. Studies published from 1999 to present will be considered for inclusion in this review, as 1999 was the year that human subject testing began using dexmedetomidine.4

The published databases to be searched include:

CINAHL

MEDLINE (Ovid)

Web of Science

EMBASE

Cochrane Control Register of Clinical Trials.

The search for unpublished studies will include:

ProQuest Theses and Dissertations, Centers for Disease Control, National Institute for Health, scientificamerican.com, clinicaltrialslocator.com, clinicalconnection.com and http://www.clinicaltrials.gov. These will be searched for reports, non-independent research or other documents produced and published by government agencies, academic institutions and other groups that are not distributed or indexed by commercial publishers and unpublished scholarly papers.

Initial keywords include spinal anesthesia, bupivacaine, dexmedetomidine, elective surgical patients, intrathecal, pain level and pain scale.

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 extraction

Quantitative 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 will be extracted by the primary (SP) and secondary (LB) reviewers independently before discussing or exchanging any opinions to facilitate accurate and reliable data entry. The authors of primary studies will be contacted for missing or unclear data.

Data synthesis

Quantitative papers 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 based on the different quantitative study designs included in this review. Where statistical pooling is not possible, the findings will be presented in narrative form including tables and figures to aid in data presentation where appropriate.

Acknowledgements

The current systematic review will partially contribute to the Doctor of Nursing Practice degree award for Stephanie Sanvi at Louisiana State University, Health Sciences Center, School of Nursing.

Appendix I: MAStARI appraisal Instrument

Appendix II: MAStARI data extraction instrument

References