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Efficacy of heads‐up CPR compared to supine CPR positions: Systematic review and meta‐analysis

Abstract Background and Aim Cardiopulmonary resuscitation (CPR) in full‐coded patients requires effective chest compressions with minimal interruptions to maintain adequate perfusion to the brain and other vital organs. Many novel approaches have been proposed to attain better organ perfusion compared to traditional CPR techniques. The purpose of this review is to investigate the safety and efficacy of heads‐up CPR versus supine CPR. Methods We searched PubMed Central, SCOPUS, Web of Science, and Cochrane databases from 1990 to February 2021. After the full‐text screening of 40 eligible studies, only seven studies were eligible for our meta‐analysis. We used the RevMan software (5.4) to perform the meta‐analysis. Results In survival outcome, the pooled analysis between heads‐up and supine CPR was (risk ratio = 0.98, 95% confidence interval [CI] = 0.17–5.68, p = 0.98). The pooled analyses between heads‐up CPR and supine CPR in cerebral flow, cerebral perfusion pressure and coronary perfusion pressure outcomes, were (mean difference [MD] = 0.10, 95% CI = 0.03–0.17, p = 0.003), (MD = 12.28, 95% CI = 5.92–18.64], p = 0.0002), and (MD = 8.43, 95% CI = 2.71–14.14, p = 0.004), respectively. After doing a subgroup analysis, cerebral perfusion was found to increase during heads‐up CPR compared with supine CPR at 6 min CPR duration and 18 to 20 min CPR duration as well. Conclusion Our study suggests that heads‐up CPR is associated with better cerebral and coronary perfusion compared to the conventional supine technique in pigs' models. However, more research is warranted to investigate the safety and efficacy of the heads‐up technique on human beings and to determine the best angle for optimization of the technique results.


| INTRODUCTION
Cardiopulmonary resuscitation (CPR) requires effective and timely chest compressions with minimal interruptions to maintain adequate organ perfusion and hence prevent irreversible organ damage. In 2019, the American Heart Association estimated around 356,000 cases of out-of-hospital cardiac arrest (OHCA) as well as 209,000 cases of in-hospital cardiac arrest. Unfortunately, only 8.4% of OHCA exhibited satisfying neurological outcomes upon hospital discharge. 1 In successfully resuscitated patients, anoxic brain injury served as the most common cause of death after an OHCA. Therefore, an effective CPR technique is critical to improve cerebral blood flow and reduce irreversible brain damage in post-cardiac arrest patients. 2 Compared to traditional CPR techniques, novel approaches were designed to ensure continued blood flow to the brain and vital organs. 3 They entail head and chest elevation to enhance blood return to the heart by gravity. This would seem counterintuitive with the blood being taken away from the brain. When considering passive leg raising techniques used to increase preload to the heart, it would make sense that elevating the head would work along the same lines. One significant difference between these two approaches is that blood pooled in the brain causes pressure due to the skull compartment. Intracranial pressure elevation can cause brain damage, making brain venous runoff a critical consideration. 3 Patients were shown to benefit from being in an elevated position during transport and CPR. Recent research suggests reducing stretcher length could allow for manipulation of the patient's body and maximize the delivery of high-quality CPR. 4 Several emergency medical service (EMS) systems in the United States have adopted head elevation techniques among other advances and resulted in raised resuscitation and survival rates for all arrested patients. 5 A very good EMS system example is the one adopted in Palm Beach County, Florida which raised resuscitation rates for all patients from 18% to 34% and from 23% to more than 44% among those with ventricular fibrillation (VF)/ventricular tachycardia arrests. [5][6][7] We aim to provide a thorough review of the utility and feasibility of the heads-up CPR technique as well as the necessary training and equipment to perform successful CPR.

| METHODS
We conducted this systematic review according to the guidelines of the Cochrane handbook for systematic reviews and meta-analysis.
We also followed the criteria of the preferred reporting items of systematic reviews and meta-analysis (PRISMA Statement) during this review preparation.

| Search strategy
We searched PubMed Central, SCOPUS, web of science, and Reviewers independently screened the titles and abstracts of the trials, followed by the full-text screening for confirmation to include the articles in our study.

| Data extraction
Authors were divided into two groups to extract data from the included studies: (1) summary including study design, groups, and sample size (name and number of each group), results and (2) outcomes including Coronary perfusion pressure (mmHg), cerebral perfusion pressure (mmHg), cerebral flow (ml/min), coronary blood flow (ml/min), systolic, and diastolic aortic pressure and survival.

| Risk of bias assessment
We used the Cochrane Risk of Bias tool provided in the Cochrane handbook for systematic reviews of interventions. The domains included were 1 : Random sequence generation (selection bias). 2 Allocation concealment (selection bias). 3 Blinding of participants and personnel (performance bias). 4 Outcomes assessment (detection bias). 5 Incomplete outcome data (attrition bias). 6 selective reporting (reporting bias). 7 Other potential sources of bias. The reviewers judged the domains as: "low risk," "high risk," or "unclear."

| Data analysis
We used the RevMan software (5.4) to perform the metaanalysis; the continuous outcomes were measured as mean difference (MD) and standard deviation (SD), and the dichotomous outcomes as risk ratios (RR) with 95% confidence interval (CI). In case of heterogeneity detected by the I-square test over 50%, we used "leave-one-out" in general; the results were considered significant if the p < 0.05.

| Study inclusion
After a search of the literature, 956 publications resulted and then became 537 after the removal of duplicates. Of these, 18 were eligible for full-text screening. After the full-text screening, seven studies were included in our meta-analysis, as shown in ( Figure 1). Survival, cerebral flow, cerebral perfusion pressure, coronary perfusion pressure, systolic aortic pressure, and diastolic aortic pressure outcomes were reported in 3, 4, 4, 6, 5, and 6 studies, respectively. The "Ryu 2016" study was divided into two lessons because the trial was on two groups of pigs. The risk of bias assessment and summary of the included studies are shown in Figure 2 and Table S1, respectively. The overall bias was moderate in the included studies as we found bias in blinding of outcome assessment (detection bias) and incomplete outcome data (attrition bias) domains in only two studies and some other biases. We found no significant bias in random sequence generation (selection bias), allocation concealment (selection bias), blinding of participants and personnel (performance bias), and selective reporting (reporting bias).

| Analysis
The total number of pigs included in the meta-analysis in the headsup CPR group is 67 pigs, and the total number of pigs in the supine CPR group is 77 pigs.
In survival outcome, the pooled analysis between heads-up and supine CPR was (RR = 0.98, 95% CI = 0.17-5.68, p = 0.98), we observed heterogeneity that was not solved by leave-one-out test, as shown in Figure 3.

| The origin of heads-up CPR and bundle approach
The conventional passive CPR method delivers a small percentage of baseline cardiac output, leading to inadequate perfusion of the heart and brain. 8,9 Due to these downfalls, Dr. Lurie developed a technique that increased venous return by elevating the chest during decompression intervals. This modification utilized direct contact via suction cups resulting in active compression-decompression (ACD) CPR. 10 Additionally, elevating the head and chest of the patient during CPR increased blood flow to the brain while also increasing the venous runoff. 11 Improved cerebral perfusion pressure (CerPP) was simply due to increased mean aortic pressure and decreased intracranial pressure (ICP) in the heads-up CPR group. 11 With head elevation, venous blood rapidly drains from the brain to the heart, reducing ICP and lowering the arterial and venous pressure waves. 12 In the bundle approach of CPR, the synergistic effects of head and neck elevation result in the most significant improvement of cerebral and coronary perfusion pressures (CoPP). 13 This new bundle approach showed its efficacy in improving rates of return of spontaneous circulation (ROSC) and sustained circulation when used in pre-hospital cardiac arrest care plans. 5 Greater rates of ROSC are associated with a higher coronary perfusion pressure value. 14,15 group. 16 Prolonged CerPP remained significantly higher in the headsup CPR pigs at 22 min than flat pigs in the ACD + threshold device (TD) and standard CPR groups. 16 Notably, the CerPP was markedly higher in animals receiving heads-up ACD + TD CPR compared with heads-up standard CPR. No pigs treated with traditional CPR achieved successful resuscitation. 17 Moore et al. 11 implemented an experiment in pig models to assess the efficacy of heads-up CPR on hemodynamics. They CerPP elevation as when utilized in adjunct. 13,16 When not used in combination with the whole-body tilt positioning, the mean aortic pressure decreased during the initial automated CPR. 10 With the head elevation in the bundle of controlled automated reperfusion of the whole body, providers observed a neurologic benefit despite 20 min of no-flow time. 22 Such conflicting findings demonstrate the need for more rigorous human trials to assess the utility and peak angles of cerebral blood flow, coronary blood flow, morbidity, and mortality. Such studies may lead to decreased morbidity and mortality in patients' post-headsup CPR. It is reasonable to consider the approach of heads-up CPR performance so that blood pooling in the extremities can be avoided by maintaining the vertical "uphill" aortic drive during elevation. 23 However, preliminary findings seem to suggest the idea that the prone position for legs accompanied by head and torso elevation may be more ideal. 5,24 CPR performed in the whole-body heads-up over a long period precipitates dangerous venous blood pooling in the lower extremities by gravity, 16 decreasing blood to the heart. It has been suggested that to overcome the venous pooling during heads-up CPR; a tourniquet-assisted device may be implemented to overcome the pooling. 25 To improve the hemodynamics of patients in cardiac arrest, the performance of passive leg raising was shown to be unfavorable. 25,26 Neurological outcome improvements should be explored further in the context that increased sustained brain perfusion will ultimately lead to protection from reperfusion injury during CPR. Simply put, if the brain remains perfused, it would not need to get re-perfused, lowering the potential brain damage. For example, a study showed that 11 of 25 pigs in the heads-up group showed zero neurological impairment a week after CPR, whereas only 5 of the 20 in the supine model had the same result. 22 Furthermore, brain injury arising in the arterial and venous blood vasculature pressure via each compression has also been decreased with head elevation. 13,27 The idea of "priming the pump" has also been suggested when attempting the heads-up CPR technique with the ITD utilized where you first begin the CPR in the supine position before transferring the patient to the elevated heads-up position. 22,28 The idea of elevation CPR "priming" has been further suggested to gradually increase the elevation level, again, with the utility of synchronized Use of the ITD. 11,22,23 During the performance of CPR, when the head is placed in the heads-up position, and the director is elevated too rapidly, it poses a danger because the aortic pressure may quickly decline due to gravity.

| Downfalls of heads-up CPR model
Therefore, CPR should not be interrupted when the head is elevated. 23 The

| CONCLUSION
We found a statistically significant association between increased cerebral flow and heads-up CPR position, as compared to supine CPR position. However, no difference in survival was detected between the two techniques. More research is required to get conclusive evidence about the efficacy of heads-up CPR compared to supine CPR positions in humans and to determine the effect of variables such as the automated device and level of head elevation on the outcomes of the CPR. writing-review & editing. All authors have read and approved the final version of the manuscript. Jaffer Shah had full access to all of the data in this study and takes complete responsibility for the integrity of the data and the accuracy of the data analysis.

ACKNOWLEDGMENTS
We would like to thank David Murry for his expertise on the top, as well as his mentoring and guidance throughout the entire process.
This study did not receive any funding.

CONFLICTS OF INTEREST
The authors declare no conflicts of interest.