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Effects of preoperative intrathecal morphine on postoperative intravenous morphine dosage

a systematic review protocol

Pitre, Luke; Garbee, Deborah; Tipton, Julia; Schiavo, Julie; Pitt, Andrew

JBI Database of Systematic Reviews and Implementation Reports: April 2018 - Volume 16 - Issue 4 - p 867–870
doi: 10.11124/JBISRIR-2016-003209

Review question/objective: The purpose of this systematic review is to describe the effect of preoperative intrathecal morphine (ITM) on postoperative intravenous (IV) morphine dosage during the first postoperative day. This systematic review will compare the postoperative IV morphine dosage of patients receiving ITM plus morphine morphine-based patient-controlled analgesia (PCA), to patients receiving PCA morphine without ITM. This will establish the magnitude of the postoperative morphine sparing effect of ITM.

This review aims to answer the following specific question: In adult abdominal and thoracic surgery patients undergoing general anesthesia (GA), what is the effect of ITM plus PCA morphine, compared to PCA morphine alone, on total IV morphine dosage (in milligrams) during the first 24 hours after surgery?

Louisiana Centre for Promotion of Optimal Health Outcomes: a Joanna Briggs Institute Center of Excellence

Correspondence: Luke Pitre,

There is no conflict of interest in this project.

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Postoperative pain is a major concern of anesthesia providers and their patients, yet surgical patients often experience inadequately controlled postoperative pain. Acute postoperative pain affects up to 80% of patients and adequate pain control is achieved in less than 50% of patients.1 Patients undergoing major abdominal or thoracic surgeries often report severe pain of seven or eight out of 10 on a numeric rating scale.2 Uncontrolled postoperative pain is associated with delayed resumption of physical activity, reduced patient satisfaction and increased risk of developing chronic pain syndromes.3 Patients with adequate postoperative analgesia are able to begin recovery more quickly and experience fewer negative outcomes.4

Intravenous (IV) opioids, the most common treatment for postoperative pain, often provide insufficient analgesia in adult abdominal and thoracic surgery patients when used alone. Inadequate analgesia has also been noted with patient-controlled analgesia (PCA), and large doses of IV opioids have been associated with respiratory depression, nausea and pruritus, whether administered directly by healthcare providers or via PCA.5 Other common medications used to treat acute postoperative pain include IV acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDS). While effective, these medications are not appropriate for all patients. Anesthesia providers often avoid the use of acetaminophen in patients with liver disease, and NSAIDS such as ketorolac are usually avoided in patients with renal disease or when bleeding is a concern.

Intrathecal morphine (ITM) offers an additional option for achieving postoperative analgesia. The technique involves a preoperative injection of morphine into the cerebrospinal fluid, which activates Mu-opioid receptors located in the dorsal horn of the spinal cord. Morphine is particularly well suited to intrathecal analgesia because it is relatively hydrophilic, compared to other opioids such as fentanyl, allowing for a longer residence in the cerebrospinal fluid and increased duration of action.6 While large doses of ITM are associated with side effects similar to IV morphine, the intrathecal route requires much smaller doses compared to IV morphine. One randomized controlled trial (RCT)5 of adult patients undergoing reduction mammoplasty found that patients receiving ITM doses of 200mcg required 11 mg PCA morphine over 24 hours for adequate postoperative analgesia. Patients in the same study who did not receive ITM required 45 mg of PCA morphine over the same period. There was no difference in adverse events between the two groups.

Quantification of the IV morphine sparing effect of ITM in the proposed population would help anesthesia providers determine if ITM is appropriate for their individual patients.6 For example, if ITM produces only a small or clinically insignificant reduction in IV morphine requirements for a given surgical procedure, the anesthesia provider may choose PCA morphine alone or a different form of postoperative analgesia. In order to quantify this value, the effect of ITM on IV morphine dosage must be examined.

A search of CINAHL, MEDLINE, Cochrane Library, and the JBI Database of Systematic Reviews and Implementation Reports yielded one systematic review and meta-analysis6 that evaluated the degree and duration of analgesia, adverse effects and dose responsiveness of ITM in adult patients receiving general anesthesia (GA) for abdominal, thoracic, orthopedic and spinal surgery. Twenty-seven RCTs were included with 645 patients receiving ITM and 560 patients receiving a placebo. The meta-analysis reported that ITM is effective at reducing PCA opioid requirements during the first 24 hours after surgery. However, this systematic review proposal differs from the previously conducted systematic review and meta-analysis6 in several ways. First, this proposal includes additional databases, including, CINAHL, ProQuest Dissertations and Theses, and Scopus. Second, the inclusion criteria also differ because this proposal includes studies with patients who were extubated immediately after surgery as well as studies that utilized PCA with morphine only. Lastly, the previous systematic review and meta-analysis6 included RCTs published up to 2007. The ability of ITM to reduce postoperative IV morphine requirements is the subject of continued and vigorous study. The ability to include updated data, as well as differences in search strategy and inclusion criteria, differentiates this proposal from the previous systematic review and meta-analysis published in 2009.6

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Inclusion criteria


This review will consider studies that include patients 18 years of age or over receiving GA for thoracic or abdominal surgeries. Patients under 18 years of age will be excluded due to differences in the treatment of pain in children. Patients receiving intrathecal local anesthetic in addition to ITM will also be excluded. Patients must be able to use PCA and be extubated immediately after surgery.

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This review will consider studies that evaluate the effect of any single dose of preoperative ITM compared to no preoperative ITM on total dosage of postoperative IV PCA morphine (in milligrams) administered during the first 24 hours after surgery.

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This review will consider studies that include the following outcome measure: total PCA morphine dosage measured in milligrams administered during the first 24 hours after surgery.

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Types of studies

This review will consider experimental studies including RCTs and pseudo-RCTs as well as retrospective chart reviews.

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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 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. Thirdly, the reference list of all identified reports and articles will be searched for additional studies. Studies published in English will be considered for inclusion in this review. Studies published from 1984 to the present will be included in this review. Even though ITM was first reported in 1979,7 PCA was only reported in the literature from 1984.8

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Information sources

The databases to be searched include: CINAHL, Cochrane Central Register of Controlled Trials, Embase,, MEDLINE, ProQuest Dissertations and Theses, Scopus.

Initial keywords to be used will be: intrathecal, morphine, postoperative, pain, PCA, patient controlled analgesia, general anesthesia.

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Assessment of methodological quality

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 System for the Unified Management, Assessment and Review of Information (JBI SUMARI).9 Studies that scored with a “yes” for questions 1, 6, 7, 8, 9, and 10 by two independent reviewers will be included in the review. Questions regarding blinding will be excluded due to ethical issues of administering an invasive placebo. The remaining questions will address randomization and treatment of experimental versus control groups. Any disagreements that arise between the reviewers will be resolved through discussion, or with a third reviewer. The results of the methodological quality assessment will be reported in accordance with the recommendations of The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA).10

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Data extraction

Quantitative data will be extracted from papers included in the review using the standardized data extraction tool from JBI SUMARI.9 The data extracted will include specific details about the interventions, populations, study methods and outcomes of significance to the review question and specific objectives.

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Data synthesis

Quantitative papers will, where possible, be pooled in statistical meta-analysis using JBI SUMARI.9 All results will be subject to double data entry. Effect sizes expressed as weighted mean differences (for continuous data) and their 95% confidence intervals will be calculated for analysis. Statistical heterogeneity will be assessed using the standard Chi-square and I-square values, and clinical heterogeneity will be explored using subgroup analysis based on type of surgery 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.

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Appendix I: Search strategy

CINAHL/EBSCOHost (searched on August 2, 2016)



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1. Chou R, Gordon DB, de Leon-Casasola OA, Rosenberg JM, Bickler S, Brennan T, et al. Assessment of pain. Br J Anaesth 2008; 101 1:17–24.
2. Jaffe RA, Stanley SI, Schmiesing CA, Golianu B. Anesthesiologist's manual of surgical procedures. 4th ed.Baltimore, MD: Wolters Kluwer; 2014.
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5. Karamese M, Akdag O, Kara I, Yildiran GU, Tosun Z. The comparison of intrathecal morphine and IV morphine PCA on pain control, patient satisfaction, morphine consumption, and adverse effects in patients undergoing reduction mammoplasty. Eplasty 2015; 15 (e15):126–134.
6. Meylan N, Elia N, Lysakowski C, Tramer M. Benefit and risk of intrathecal morphine without local anaesthetic in patients undergoing major surgery: Meta-analysis of randomized trials. Br J Anaesth 2009; 102 2:156–167.
7. Bujedo BM. A clinical approach to neuraxial morphine for the treatment of postoperative pain. Pain Res Treat 2012; 2012 612145:1–11.
8. Lehmann KA. Recent developments in patient-controlled analgesia. J Pain Symptom Manage 2005; 29 (5S):S72–S89.
9. The Joanna Briggs Institute. The Joanna Briggs Institute Reviewers’ Manual: 2014 edition. Australia: The Joanna Briggs Institute; 2014.
10. Moher D, Liberati A, Tetzlaff J, Altman DG. The PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 2009; 6 7:e1000097.

Intrathecal morphine; patient controlled analgesia; postoperative pain

© 2018 by Lippincott williams & Wilkins, Inc.