Background

Coronary arteries are blood vessels that supply vital oxygen and nutrients to the myocardial muscles, which are necessary for the heart to function properly. Blood flow to the coronary arteries and to the rest of the body can be restricted when (1) blood flow from the heart is reduced due to mechanical defects in heart valves1 or (2) occlusions occur in the lumen of the coronary vessels, commonly referred to as coronary artery disease.2 Surgical techniques can intervene to repair mechanical valve defects and coronary artery occlusions. Established cardiac surgery techniques include coronary artery bypass grafting (CABG) and/or valvular repair/replacement.1,3 There are instances where repairing both are warranted during the same operative period.4

Cardiac surgery is stressful on the human body, and patients undergoing cardiac surgery are sent to the cardiovascular intensive care unit (ICU) as a standard of practice due to the need for close patient monitoring. These patients remain intubated, requiring a breathing tube and sedated for mechanical ventilation due to an initial vulnerable hemodynamic state, but they are usually extubated (removal of the tube) within one to six hours postoperatively.5 The goals for a patient who is mechanically ventilated are to maintain a level of comfort without agitation, lower anxiety levels and minimize pain.5,6 Sedative agents and analgesics are commonly used in postoperative cardiac surgery patients to achieve these goals. Proper sedation and analgesia can adequately provide comfort, which in turn can facilitate sufficient mechanical ventilation.5 There are several sedative agents that are available for use, but each class of drug has distinct pharmacokinetic and pharmacodynamic properties that elicit different side effects.5 Selection of a sedative agent is determined by its mechanism of action, onset of action, duration of action and termination of action of the drug along with other properties which may be unique to that drug. Dexmedetomidine (Precedex(TM), Hospira, Inc., Lake Forest, IL, USA) and propofol (Diprivan(TM), Fresenius Kabi USA, LLC, Lake Zurich, IL, USA) are two commonly used sedative agents and have distinct pharmacologic characteristics that make them appealing in this patient population.5,6

Propofol is commonly used in the ICU for short-term (less than 24 hours) sedation in ventilated patients postoperatively.7 Propofol is an intravenous phospholipid emulsion that has anesthetic, sedative and hypnotic properties and was approved in 1993 by the United States Food and Drug Administration for use as a sedative in mechanically ventilated patients.8 It has been used as a standard for sedation because of its properties of rapid onset, short duration of action and relatively low cost; however, the adverse effects of propofol are concerning, especially in cardiovascular patients.9,10 These adverse effects include but are not limited to bradycardia, hypotension and respiratory depression.6 Although propofol may produce hemodynamic instability, it still has ideal pharmacokinetic properties for patients requiring short-term sedation. A 2009 propofol shortage in the United States led to increased use of dexmedetomidine for sedation, which was found in some cases to facilitate extubation and shorten required times of mechanical ventilation,5,6,11 and has since been proposed as an alternative to propofol in coronary artery bypass surgery.12

Dexmedetomidine is a potent [alpha]₂-adrenoreceptor agonist with anxiolytic, sedative, analgesic and sympatholytic (reduces tachycardia and hypertension) properties, making it attractive for perioperative uses. Approved in 1999 in the United States as a continuous infusion for sedation and analgesia in the ICU, dexmedetomidine has been used to provide sedation for cardiac surgery patients transitioning from the operating room to the ICU before extubation.13,14 Continuous infusion of dexmedetomidine produces a sedative/hypnotic state that resembles natural sleep but does not interfere with the normal course of ventilator weaning and extubation because it does not suppress the respiratory drive or decrease the arterial oxygen saturation.7,15 Subsequently, sedation with dexmedetomidine could promote early extubation. The most concerning side effects of dexmedetomidine are bradycardia and hypotension due to its sympatholytic properties, thus necessitating its careful use in vulnerable patient populations for whom these effects would not be tolerated.14

The use of mechanical ventilation, independent of indication, is associated with an increased likelihood of complications, such as pneumonia, ventilator-induced lung injury and increased cost,16 and long-term (greater than seven days) mechanical ventilation increases the risk of morbidity and mortality.17 As patients recover and their independent ventilatory capability and the demand for mechanical ventilation decrease, it is advantageous to withdraw these patients from mechanical ventilation as early as possible. Early extubation is a key component to reducing complications relating to long-term mechanical ventilation, and development of early extubation protocols may be of value to practitioners as it may help reduce the patient's length of stay (LOS) in the ICU and in the hospital, resulting in decreased hospital costs and ultimately improved patient outcomes.18 Extended LOS in the ICU increases the risk for development of delirium with subsequent adverse events,5 and ICUs have a higher overall risk of infection when compared with the general floors.19 Total hospital LOS itself is associated with more costly care and increased incidence of postoperative complications.20 The use of dexmedetomidine or propofol may also affect hospital mortality rate due to the hemodynamic implications attributed to their pharmacodynamics. Hospital mortality rates are a major concern to practitioners as it may guide their clinical decisions toward a safer approach in patients' plan of care.

Dexmedetomidine, although fairly new, has been accepted and expanded for use in postoperative cardiac surgery patients. The unique properties of dexmedetomidine make it desirable in postoperative cardiac surgery patients because it lacks the effects of respiratory depression, has potential for decreased opioid use and functions as a sympatholytic. These favorable characteristics could lead to patients having decreased times to extubation, decreased ICU-LOS and overall decreased hospital LOS.6 Although propofol is still widely used as a postoperative sedative, recent randomized controlled trials and retrospective studies comparing the effects of dexmedetomidine compared to propofol on times to extubation in postoperative adult cardiac surgery patients support dexmedetomidine as an effective alternative drug choice for short-term postoperative sedation for mechanical ventilation.5,6,7,11,12 However, studies comparing the drugs' effects on ICU LOS, total hospital LOS5,6,12 and mortality rates5,6 have showed conflicting results.

An initial search of PubMed, Embase, Joanna Briggs Database of Systematic Reviews and Implementation Reports, Cochrane Library of Systematic Reviews, PROSPERO and EPISTEMINIKOS was conducted to locate any published systematic reviews or systematic review protocols on the proposed topic. No existing systematic review report or review protocol was found that specifically investigated the effect of dexmedetomidine compared to propofol on time to extubation, ICU and hospital LOS, nor mortality following cardiac surgery. A meta-analysis published in 2012 reviewed dexmedetomidine for postoperative cardiac surgery patients in terms of times to extubation, ICU and hospital LOS, and mortality,21 but lacked homogeneity in its control group by comparing dexmedetomidine as the interventional group with multiple and varied sedation regimens for analyzing effect on length of mechanical ventilation, including regimens of propofol, morphine, midazolam, lorazepam or a combination of these. The lack of homogeneity in the analysis may ultimately confound findings regarding extubation times when comparing dexmedetomidine and propofol. The proposed protocol is distinct by only comparing dexmedetomidine and propofol in this population and thus improving homogeneity in its analysis. The review will investigate the effects of dexmedetomidine and propofol on extubation times, total length of ICU stay, total length of hospital stay and mortality rates.

Inclusion criteria

Types of participants

The current review will consider studies that include participants of any gender or ethnicity who are >=18 years of age, undergoing valvular surgery, CABG surgery, or valvular surgery and CABG. Any study that includes pediatric cardiac surgery will be excluded. Furthermore, any study with participants not undergoing cardiac surgery will be excluded.

Types of intervention(s)

The current review will consider studies that compare only dexmedetomidine and propofol for sedation after cardiac surgery.

Any study will be considered if propofol or dexmedetomidine are used as continuous infusions and not as bolus dosing. Studies will be excluded if participants have received both dexmedetomidine and propofol concurrently as a primary sedation. All variations of dosages and duration of both sedative agents will be included. The administration times of the sedative agents will not be limited to the postoperative period but will also include the perioperative period.

Outcomes

The current review will consider studies that include the following outcomes: total time (minutes) of mechanical ventilation after cardiac surgery, specifically from end of surgery to extubation; total length of ICU stay (days) following cardiac surgery, specifically from ICU admission to transfer to medical ward; total length of hospital stay (days) following cardiac surgery, from date of admission to date of discharge and in-hospital mortality (rates), from date of admission to date of discharge.

Types of studies

The current review will consider randomized controlled trials, controlled trials and prospective and retrospective cohort studies for inclusion.

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 (PubMed) and EMBASE will be undertaken followed by an 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 the English language will be considered for inclusion in this review. Studies published from 1999 to the present date will be considered for inclusion in this review. Dexmedetomidine was approved in the United States for continuous infusion for sedation in the ICU in 1999 and in other countries thereafter.14

The databases to be searched include:

MEDLINE (PubMed)

Embase

Trip Database

ProQuest Nursing and Allied Health Source Database

Web of Science.

The search for unpublished studies will include:

ProQuest Dissertations and Theses

MEDNAR.

Initial keywords to be used will be: cardiac surgery OR heart surgery OR thoracic surgery, dexmedetomidine, propofol, extubation OR detubation, mechanical ventilation OR artificial ventilation OR artificial respiration, length of stay OR hospitalization, mortality

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 Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) (Appendix I). Any disagreements that arise between the reviewers will be resolved through discussion.

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. Authors of primary studies will be contacted for missing information or to clarify unclear data.

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 or standard mean difference (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 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 is being conducted as partial fulfillment of the requirements for a Doctor of Nursing Practice (DNP) degree as established by the Texas Christian University School of Nurse Anesthesia.

Appendix I: Appraisal instruments

MAStARI appraisal instrument

Appendix II: Data extraction instruments

MAStARI data extraction instrument

References