Hemodynamic, laparoscopic, magnesium sulfate, pneumoperitoneum



  1. Nygard, Brian
  2. Brickey, Doug
  3. Greenwood, Jennifer


Objective: The objective of this systematic review is to determine the efficacy of intravenous magnesium sulfate when used to attenuate hemodynamic fluctuations associated with the creation of pneumoperitoneum in adults undergoing laparoscopic surgery.


Introduction: Laparoscopic surgery has gained popularity as a result of improved patient outcomes postoperatively, but pneumoperitoneum alters the patient's physiology and hemodynamic profile during the intraoperative period. Magnesium sulfate is a non-opioid agent known for its ability to blunt the physiologic sympathetic response associated with exposure to noxious stimuli. Magnesium sulfate may be efficacious in combating undesirable hemodynamic changes associated with pneumoperitoneum.


Inclusion criteria: Studies that included participants 18 years or older undergoing any laparoscopic surgery using pneumoperitoneum with CO2 insufflation will be considered. Studies will be excluded if patients were being treated for pheochromocytoma. Studies can employ any intravenous dosing strategy of magnesium sulfate, administered at any point in the perioperative period for the purpose of blunting the sympathetic response to creation of a pneumoperitoneum.


Methods: A systematic search of MEDLINE, CINAHL, Cochrane Library, Google Scholar, Trip Database, MedNar, Grey Literature Report and ProQuest Dissertations and Theses will be conducted to identify both published and unpublished studies on the topic of interest. The search will be limited to studies written in English and performed on humans. Studies will be selected for review based on inclusion criteria and will be appraised by two reviewers using a standardized appraisal tool.


Systematic review registration number: PROSPERO CRD42019139991.


Article Content


Changes in health care and reimbursement strategies have pressured providers to strategize how surgical recovery could be enhanced to promote early return to baseline function and reduce hospital length of stay. One way this can be accomplished is through minimally invasive surgical techniques. Minimally invasive laparoscopic procedures have revolutionized surgery by improving both patient and surgical outcomes.1 For example, reduced pain via the minimally invasive approach promotes early ambulation, early return to activities of daily living and shorter hospital stays.1 Through the use of a laparoscopic approach, surgeries that have previously required inpatient stay are becoming routinely performed on an outpatient basis. This minimally invasive approach is also used for a variety of conditions that require surgical intervention, resulting in over 3.5 million laparoscopic procedures being performed annually in the United States.2 Despite the minimally invasive nature of the laparoscopy, it continues to disrupt the body's protective mechanisms and alters the patient's hemodynamics.3


Historically, opioids were the primary agent used to blunt surgical pain and hemodynamic changes in response to surgical stimuli.4 Opioids work to blunt the hemodynamic response to intubation and surgical stimulation through activation of the mu-receptors in the higher brain centers, such as the periaqueductal gray and rostroventral medulla, that are responsible for modulation of noxious stimuli in the dorsal horn of the spinal cord.5 Due to their ubiquitous use, opioid-related deaths have increased exponentially from 1999 to 2015, as evidenced by a 30% increase in opioid-related deaths from 2015 to 2016.6 Magnesium sulfate has been investigated as an alternative method for mitigating postoperative pain while minimizing systemic side effects. Previous systematic reviews have successfully demonstrated the efficacy of intravenous magnesium sulfate as an opioid sparing agent.7-9


In addition to surgical pain management, anesthesia providers are concerned with maintaining hemodynamic stability. Many factors contribute to hemodynamic changes in the perioperative period including intubation, airway manipulation, incision, emergence and the formation of the pneumoperitoneum. The purpose of pneumoperitoneum is to facilitate visualization of the surgical field when using the laparoscopic approach, which is achieved through the use of carbon dioxide (CO2) gas insufflated into the abdomen.1 However, pneumoperitoneum is associated with common hemodynamic changes such as an increased heart rate (HR), mean arterial pressure (MAP) and systemic vascular resistance (SVR) due to the release of catecholamines and vasopressin.10,11 In addition to the endogenous catecholamine response, external forces such as exaggerated patient positioning, derangements in respiratory status related to body habitus or any circumstance that leads to excessive pressure on the abdominal wall can result in a net reduction of cardiac output, thereby causing an increase in cardiopulmonary workload.12 Depending on pre-existing comorbidities, the increase in cardiopulmonary workload can be detrimental to patient outcomes. Wide fluctuations in HR and MAP place patients at an increased risk for myocardial ischemia, myocardial infarction, stroke and an increase in intraoperative blood loss.13 The use of an adjunct anesthetic agent that reduces perioperative opioid requirements, while also promoting hemodynamic stability, could potentially improve outcomes impacted by adverse opioid side effects and cardiopulmonary strain.


Magnesium is the fourth most common cation in the human body and functions in many capacities to maintain homeostasis.14 One of the functions of magnesium is to antagonize calcium. Calcium is also critical in many physiological functions, but excess calcium can prove detrimental to patients under anesthesia and patients with unfavorable cardiopulmonary function. As magnesium antagonizes calcium, it can serve as a protectant during the release of norepinephrine to prevent increases in HR and vasoconstriction that lead to an increased afterload and workload on the left heart.15 In addition to decreasing the workload of the left heart, magnesium promotes bronchodilation and thereby improves oxygenation, decreases pulmonary airway pressures and mitigates the potential increased workload of the right heart.16 After surgery, it is common for patients to experience hypomagnesemia, and the administration of magnesium is rarely associated with adverse effects in clinical practice.14


To reduce the risks related to traditional opioid therapy, non-opioid strategies that effectively manage the hemodynamic challenges in the surgical population must be implemented. Patients undergoing laparoscopic surgeries are at unique risk for hemodynamic changes related to the sympathetic response to pneumoperitoneum. Intravenous administration of magnesium sulfate offers a potential solution for this population. Perioperative use of magnesium sulfate could provide multifactorial benefits in the laparoscopic patient population by decreasing total opioid consumption and promoting hemodynamic stability in the setting of sympathetic response to pneumoperitoneum.10


Intravenous magnesium sulfate appears to be a promising non-opioid agent that could improve postoperative pain while also attenuating the hemodynamic response that occurs during creation of pneumoperitoneum in laparoscopic surgery. To assist in a practice transition to opioid-free/opioid-sparing anesthesia and surgical techniques, the potential impact of magnesium sulfate should be examined through systematic review of the literature.


The researchers conducted a preliminary search of the relevant databases to determine whether current evidence exists to support the use of intravenous magnesium sulfate to attenuate the hemodynamic response to pneumoperitoneum in laparoscopic surgery. A preliminary search conducted through MEDLINE, the JBI Database of Systematic Reviews and Implementation Reports, Cochrane Database of Systematic Reviews, CINAHL, PROSPERO and Google Scholar yielded one systematic review related to the use of magnesium sulfate and ketamine for hemodynamic stability.17 This systematic review examined the effect of magnesium sulfate on the sympathetic response to several different types of surgery and found reduced variability in HR but no improvement in blood pressure stability. In addition, several weaknesses in this systematic review were identified. For example, the authors performed a limited search of only two databases, which yielded only six randomized controlled trials for quantitative analysis. The type of surgery was not limited to laparoscopic approach, and only two of the studies in the review were conducted on patients with pneumoperitoneum.17 The inconclusive findings of the review were further confounded by surgical factors as a result of attempting to aggregate findings from several different types of surgery. To the knowledge of the researchers of this review, no current systematic review or meta-analysis that evaluates the efficacy of magnesium sulfate on the hemodynamic response to pneumoperitoneum during laparoscopic surgery exists. It is necessary to inform the anesthesia and surgical community regarding this novel and underutilized treatment approach in this unique but prevalent population.


Review question

What is the effect of intravenous magnesium sulfate in attenuating the hemodynamic changes in adults undergoing laparoscopic surgery?


Inclusion criteria


The current systematic review will consider studies of human participants who are 18 years or older and undergoing general anesthesia for a laparoscopic procedure (emergent or elective) with CO2 insufflation. Human participants of the studies may be rated at any score (I-IV) using the American Society of Anesthesiologists Physical Status, as this is the range most clinical trials will include. Studies will be excluded if they are investigating the use of magnesium sulfate for surgical treatment of pheochromocytoma or for the attenuation of the sympathetic response solely related to laryngoscopy.



The current systematic review will consider studies that evaluate magnesium sulfate administered intravenously during the preoperative, intraoperative or postoperative phases of care via bolus, infusion or bolus with infusion. The optimal dose and timing of magnesium sulfate as an anesthetic adjunct has not been established. Studies that utilize any intravenous dose of magnesium sulfate will be considered for inclusion.



The current review will consider studies that include the administration of magnesium sulfate when compared to placebo, normal saline or other medications (i.e. clonidine, lidocaine) used as the control group. These alternative medications can be implemented during the preoperative, intraoperative or postoperative phases of care. All dosing strategies for the control or comparator groups will be considered since there is no definitive protocol for these adjunct medications when used for hemodynamic control.



The current review will consider studies that include outcomes related to perioperative hemodynamic changes with pneumoperitoneum such as systolic blood pressure, diastolic blood pressure, HR, cardiac output, SVR, MAP, intra-abdominal pressure or pulmonary/airway pressures. These hemodynamic values may be directly measured using standard hemodynamic monitors at any interval during the perioperative period. Outcomes will be reported as the observed value or recorded change from baseline of these variables among study participants.


Types of studies

The current review will consider both experimental and quasi-experimental study designs including randomized controlled trials, non-randomized controlled trials, before and after studies and interrupted time-series studies. In addition, analytical observational studies including prospective and retrospective cohort studies, case-control studies and analytical cross-sectional studies will be considered for inclusion. Studies published in English will be included. Studies published from 1984 to present will be included as this date range is correlated with the advent of magnesium administration as an anesthetic adjunct with the publication of the hallmark article on magnesium and its properties.18



The current systematic review will be conducted in accordance with the JBI methodology for systematic reviews of effectiveness evidence.19


Search strategy

The search strategy will aim to find both published and unpublished studies. An initial limited search of MEDLINE, CINAHL and Google Scholar was undertaken to identify studies in the subject area. This informed the development of a search strategy that will be tailored for each information source. The full search strategy for MEDLINE is detailed in Appendix I. The following search terms were utilized: magnesium sulfate, hemodynamics, laparoscopic surgery, perioperative and insufflation. Index terms were also used to further expand the list of search terms. The reference list of all studies selected for critical appraisal will be screened for additional studies.


Information sources

The databases to be searched include MEDLINE, CINAHL and Cochrane Central Register of Controlled Trials. The search for unpublished studies will include Google Scholar, Trip Database, MedNar, Grey Literature Report and ProQuest Dissertations and Theses. The trial registers to be searched will include


Study selection

Following the search, all identified citations will be collated and managed with EndNote X9.0 (Clarivate Analytics, Philadelphia, PA, USA) and duplicates removed. Titles and abstracts will then be screened by two independent reviewers for assessment against the inclusion criteria for the review. Potentially relevant studies will be retrieved in full and their details imported into the JBI System for the Unified Management, Assessment and Review of Information (JBI SUMARI; Joanna Briggs Institute, Adelaide, Australia). The full text of selected citations will be assessed in detail against the inclusion criteria by two independent reviewers. Reasons for exclusion of full-text studies that do not meet the inclusion criteria will be recorded and reported in the systematic review. Any disagreements that arise between the reviewers at each stage of the study selection process will be resolved through discussion, or with a third reviewer. The results of the search will be reported in full in the final report and presented in a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram.20


Assessment of methodological quality

Eligible and selected studies will be critically appraised by two independent reviewers at the study level for methodological quality in the review using the appropriate standardized critical appraisal instruments from JBI for the given studies.19 Any disagreements that arise will be resolved through discussion or with a third reviewer. Following critical appraisal, studies will not be excluded based on their methodological quality. However, the quality score for each study will be reported and considered in the synthesis of the evidence.


Data extraction

Data will be extracted from studies included in the review by two independent reviewers using the standardized data extraction tool available in JBI SUMARI.19 The data extracted will include specific details about the populations, study methods, interventions related to dosing and duration, and outcomes of significance to the review question. Any disagreements that arise between the reviewers will be resolved through discussion or with a third reviewer. Authors of papers will be contacted to request missing or additional data, where required.


Data synthesis

Studies will, where possible, be pooled in statistical meta-analysis using JBI SUMARI.19 Effect sizes will be expressed as either odds ratios (for dichotomous data) or weighted (or standardized) final post-intervention mean differences (for continuous data), and their 95% confidence intervals will be calculated for analysis. Heterogeneity will be assessed statistically using the standard Chi-squared and I-squared tests. The use of a fixed or random effects model for meta-analysis will be determined by the level of study homogeneity or heterogeneity.21


Subgroup analyses will be conducted where there are sufficient data to investigate the effect of a consistent dosing and timing regimen of the intervention. While the researchers will consider non-randomized controlled trials, additional subgroup analysis using only randomized controlled trials may be warranted. Sensitivity analyses will be conducted to test decisions made regarding whether confounding variables contributed to the effect. 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. A funnel plot will be generated to assess publication bias if there are 10 or more studies included in a meta-analysis. Statistical tests for funnel plot asymmetry (Egger test, Begg test, Harbord test) will be performed where appropriate.


Assessing certainty in the findings

A Summary of Findings will be created using GRADEpro (McMaster University, ON, Canada). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach for grading the quality of evidence will be followed. The Summary of Findings will present the following information where appropriate: absolute risks for treatment and control, estimates of relative risk and a ranking of the quality of the evidence based on study limitations (risk of bias), directness, heterogeneity, precision and risk of publication bias.


The following outcomes will be included in the Summary of Findings when available (not all studies will include all variables): systolic blood pressure, diastolic blood pressure, HR, cardiac output, SVR, MAP, intra-abdominal pressure or pulmonary/airway pressures.



The current systematic review has been developed as part of the requirements toward the completion of a DNP in nurse anesthesia for BN and DB.


Appendix I: Search strategy for MEDLINE

Search conducted: July 1, 2019



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