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Effect of Helicopter Transportation of Acute Ischemic Stroke Patients on Mortality and Functional Outcomes: A Systematic Review and Meta-Analysis

Open AccessPublished:August 11, 2022DOI:https://doi.org/10.1016/j.amj.2022.07.001

      Highlights

      • Helicopter emergency medical services (HEMS) improve outcome in acute ischemic stroke.
      • HEMS reduce disability after an ischemic stroke, thus reducing costs in rehabilitation.
      • A high-standard strategy for operative logistics of HEMS needs to be carried out.
      • HEMS reduce neurologic sequelae but still need more studies to prove mortality reduction.

      Abstract

      Objective

      The “time is brain” concept denotes the importance of the expedited transfer of patients to stroke care centers. Helicopter emergency medical services (HEMS) can reduce the time to definitive care, which could improve neurologic prognosis and reduce mortality.

      Methods

      Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, a search for randomized controlled trials, nonrandomized controlled trials, and prospective and retrospective cohort studies was performed through specific databases from inception to February 2020. Helicopter, acute stroke, and their synonyms (according to Medical Subject Headings) were included in this search. The Newcastle-Ottawa Scale was used to assess the quality of the included studies, and the Egger test was used to assess for publication bias.

      Results

      A total of 8 studies matched the inclusion criteria and were included for meta-analysis. The overall number recruited for helicopter transportation was 1,372, and for emergency standard transportation, it was 8,587. The association among HEMS and mortality was not statistically significant (odds ratio [OR] = 0.7; 95% confidence interval [CI], 0.60-1.06; P = .12). There was a significant association between good outcomes and HEMS (OR = 2; 95% CI, 1.79-2.34; P ≤ .001), and the overall poor neurologic outcome was reduced (OR = 0.52; 95% CI, 0.46-0.60; P ≤ .001).

      Conclusion

      A good neurologic outcome was higher with HEMS compared with emergency standard transportation. The mortality rate was less in the emergency standard transportation group after pooled analysis but was not significant; the reduction in a poor outcome was statistically significant.
      One of the main lessons we learned from the Second World War was helicopter transfer for health purposes. Helicopter transfer of war victims led to the appraisal of the concept of helicopter emergency medical services (HEMS).
      • Cameron PA
      • Flett K
      • Kaan E
      • Atkin C
      • Dziukas L.
      Helicopter retrieval of primary trauma patients by a paramedic helicopter service.
      HEMS accounts for 3% of overall ambulance transports.
      • Thomas SH
      • Brown KM
      • Oliver ZJ
      • et al.
      An evidence-based guideline for the air medical transportation of prehospital trauma patients.
      On average, 2.7 additional lives are saved per 100 HEMS activations.
      • Olson MD
      • Rabinstein AA.
      Does helicopter emergency medical service transfer offer benefit to patients with stroke?.
      The critical nature of medical illnesses with the concurrent lack or inaccessibility of needful medical resources is the prime reason for using air medical transfer.
      • Cameron PA
      • Flett K
      • Kaan E
      • Atkin C
      • Dziukas L.
      Helicopter retrieval of primary trauma patients by a paramedic helicopter service.
      HEMS has conferred improved survival and functional outcome among overly critical patients with traumatic brain injury and stroke.
      • Hiu T
      • Ozono K
      • Kawahara I
      • et al.
      Efficacy of the drip and ship method in 24-h helicopter transportation and teleradiology for isolated islands.
      In the context of rural settings, HEMS has a huge impact on saving lives.
      • Cameron PA
      • Flett K
      • Kaan E
      • Atkin C
      • Dziukas L.
      Helicopter retrieval of primary trauma patients by a paramedic helicopter service.
      It can also have significant clinical benefits in urban regions with high traffic congestions.
      • Leira EC
      • Stilley JD
      • Schnell T
      • Audebert HJ
      • Adams HP.
      Helicopter transportation in the era of thrombectomy: the next frontier for acute stroke treatment and research.
      The “time is brain” concept denotes the importance of the expedited transfer of patients to stroke care centers, and the latest evidence reflects the impact of this paradigm. However, in the context of acute ischemic stroke, the clear advantages of HEMS in reducing the transfer time and improving the neurologic outcome compared with ground transport are still controversial. Therefore, this systemic review and meta-analysis aimed to determine whether HEMS improved outcomes in patients with acute ischemic stroke.

      Methods

      This study followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement for the presentation of the systematic reviews and meta-analyses and the Cochrane manual of systematic reviews and meta-analysis.

      Search

      A search for randomized controlled trials, observational studies, and prospective and retrospective studies was performed through SCOPUS (until February 2020), the Cochrane Central Register of Controlled Trials (The Cochrane Library, until February 2020), MEDLINE (Ovid, until February 2020), Embase (Ovid), and PubMed (http://www.ncbi.nlm.nih.gov/sites/entrez, until February 2020), in addition to the reference lists of the included studies, other relevant data, and potentially eligible studies. The terms used included helicopter, acute stroke, and their synonyms (according to Medical Subject Headings).

      Inclusion Criteria

      The studies to be included were screened separately for patients with acute ischemic stroke. We included prospective and retrospective experimental (trials) and observational (cohort, cross-sectional, and case-control) studies that documented mortality and functional prognosis (eg, the modified Rankin scale [mRS] or the Glasgow Outcome Scale [GOS]). We included all full-text English- and Spanish-language studies and also included any potential study from the reference list that met the criteria. We excluded studies with pediatric patients (< 18 years old), patients exposed to traumatic events, and patients with other non–stroke-related diseases and case reports.

      Evaluation of the Quality of the Studies Included

      The quality of the included studies was assessed through the Newcastle-Ottawa Quality Assessment Scale.
      • Stang A.
      Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses.
      All studies were rated as “high” methodologic quality if they scored 6 or above in the Newcastle-Ottawa Quality Assessment Scale. Those with scores of 4 to 5 were considered of moderate methodological quality, and those with scores less than 4 were considered of lower methodological quality. The Egger test was applied to evaluate the risk of publication bias.

      Data Extraction, Management, and Statistical Analysis

      The following data were extracted: mortality, good functional outcome defined as an mRS score of 0 to 3, Glasgow Outcome Scale score of 4 to 6, and data were sorted into groups (ie, helicopter transport and emergency standard transportation [ground or river ambulance]). The authors of the included studies were contacted if any relevant data were missing. Statistical analysis was performed through the odds ratio (OR) with the Mantel-Haenszel methodology for dichotomous variables with a randomized effect analysis model calculated using MedCalc 19.2.1 (Ostend, Belgium) version software. Heterogeneity was assessed by calculating chi-square (I2). We analyzed the studies by OR for each outcome with 95% confidence intervals (CIs) and a random effects model. The fixed effect model assumes that each study is estimating the same intervention effect, and the random effect model assumes that estimated intervention effects are not all the same but follow a normal distribution across studies. Data were extracted, and the helicopter transport effect on OR for mortality or functional outcome was compared with ground transport. This was extracted from text or tables or was calculated from figures when necessary.

      Results

      Studies Included

      After performing a search and excluding studies that did not meet our criteria, we identified 8 studies (Fig. 1) to be included in our meta-analysis (the characteristics of the included studies are provided in Supplemental Table 1).
      • Olson MD
      • Rabinstein AA.
      Does helicopter emergency medical service transfer offer benefit to patients with stroke?.
      ,
      • Almallouhi E
      • Al Kasab S
      • Nahhas M
      • et al.
      Outcomes of interfacility helicopter transportation in acute stroke care.
      • Conroy MB
      • Rodriguez SU
      • Kimmel SE
      • Kasner SE.
      Helicopter transfer offers a potential benefit to patients with acute stroke.
      • Funder KS
      • Rasmussen LS
      • Lohse N
      • et al.
      The impact of a physician-staffed helicopter on outcome in patients admitted to a stroke unit: a prospective observational study.
      • Hesselfeldt R
      • Gyllenborg J
      • Steinmetz J
      • Do HQ
      • Hejselbaek J
      • Rasmussen LS.
      Is air transport of stroke patients faster than ground transport? A prospective controlled observational study.
      • Lukovits TG
      • Von Iderstine SL
      • Brozen R
      • Pippy M
      • Goddeau RP
      • McDermott ML.
      Interhospital helicopter transport for stroke.

      Reiner-Deitemyer V, Teuschl Y, Matz K, et al. Helicopter transport of stroke patients and its influence on thrombolysis rates: data from the Austrian Stroke Unit Registry. Stroke.2011;42:1295-1300.

      • Ueno T
      • Nishijima H
      • Hikichi H
      • et al.
      Helicopter transport for patients with cerebral infarction in rural Japan.
      Figure 1
      Figure 1The Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart of the included studies.

      Systematic Review

      In the present meta-analysis, a total of 8 studies
      • Olson MD
      • Rabinstein AA.
      Does helicopter emergency medical service transfer offer benefit to patients with stroke?.
      ,
      • Almallouhi E
      • Al Kasab S
      • Nahhas M
      • et al.
      Outcomes of interfacility helicopter transportation in acute stroke care.
      • Conroy MB
      • Rodriguez SU
      • Kimmel SE
      • Kasner SE.
      Helicopter transfer offers a potential benefit to patients with acute stroke.
      • Funder KS
      • Rasmussen LS
      • Lohse N
      • et al.
      The impact of a physician-staffed helicopter on outcome in patients admitted to a stroke unit: a prospective observational study.
      • Hesselfeldt R
      • Gyllenborg J
      • Steinmetz J
      • Do HQ
      • Hejselbaek J
      • Rasmussen LS.
      Is air transport of stroke patients faster than ground transport? A prospective controlled observational study.
      • Lukovits TG
      • Von Iderstine SL
      • Brozen R
      • Pippy M
      • Goddeau RP
      • McDermott ML.
      Interhospital helicopter transport for stroke.

      Reiner-Deitemyer V, Teuschl Y, Matz K, et al. Helicopter transport of stroke patients and its influence on thrombolysis rates: data from the Austrian Stroke Unit Registry. Stroke.2011;42:1295-1300.

      • Ueno T
      • Nishijima H
      • Hikichi H
      • et al.
      Helicopter transport for patients with cerebral infarction in rural Japan.
      were included after proper matching with the inclusion criteria (Table 1). Among the studies included, 4 were retrospective observational cohort studies, and 3 were prospective observational cohort studies that were conducted between 1996 and 2019. Reiner-Deitemyer et al

      Reiner-Deitemyer V, Teuschl Y, Matz K, et al. Helicopter transport of stroke patients and its influence on thrombolysis rates: data from the Austrian Stroke Unit Registry. Stroke.2011;42:1295-1300.

      published the largest cohort (N = 7,842, helicopter transport = 898) of patients with ischemic stroke managed with helicopter transport. The follow-up length was variable from in-hospital death to a maximum of 12 months’ duration. In this study, thrombolysis was provided in different transportation alternatives (helicopter or ground-based alternatives), and they demonstrated that being transported with HEMS was a predictor of the probability of receiving thrombolysis. Conroy et al
      • Conroy MB
      • Rodriguez SU
      • Kimmel SE
      • Kasner SE.
      Helicopter transfer offers a potential benefit to patients with acute stroke.
      pooled patients with ischemic stroke and showed only the HEMS group without comparison to standard transport (ground based). Thrombolysis was provided only before transfer to the hospital (11% of patients) because no patient met the criteria on arrival. Lukovits et al
      • Lukovits TG
      • Von Iderstine SL
      • Brozen R
      • Pippy M
      • Goddeau RP
      • McDermott ML.
      Interhospital helicopter transport for stroke.
      included patients with all-cause stroke (intracerebral hemorrhage = 44%, subarachnoid hemorrhage = 24%, subdural hematoma = 14%, isolated intraventricular hemorrhage = 2%, ischemic stroke or transient ischemic attack = 9%, and nonstroke diagnoses = 7%). Only 7 patients received thrombolysis, mostly after transportation. Olson et al
      • Olson MD
      • Rabinstein AA.
      Does helicopter emergency medical service transfer offer benefit to patients with stroke?.
      included patients with ischemic stroke and compared ground-based transportation. Most patients in both groups received thrombolysis before transfer. Hesselfeldt et al
      • Hesselfeldt R
      • Gyllenborg J
      • Steinmetz J
      • Do HQ
      • Hejselbaek J
      • Rasmussen LS.
      Is air transport of stroke patients faster than ground transport? A prospective controlled observational study.
      included patients with ischemic stroke transported through HEMS and ground-based alternatives. A similar percentage of patients treated with thrombolysis was shown in both groups. Funder et al
      • Funder KS
      • Rasmussen LS
      • Lohse N
      • et al.
      The impact of a physician-staffed helicopter on outcome in patients admitted to a stroke unit: a prospective observational study.
      included patients with ischemic stroke in the HEMS group and the ground-based group. Most patients in the ground-based group underwent thrombolysis, but in the HEMS group nearly half of the patients underwent thrombolysis. Almallouhi et al
      • Almallouhi E
      • Al Kasab S
      • Nahhas M
      • et al.
      Outcomes of interfacility helicopter transportation in acute stroke care.
      and Ueno et al
      • Ueno T
      • Nishijima H
      • Hikichi H
      • et al.
      Helicopter transport for patients with cerebral infarction in rural Japan.
      included patients with ischemic stroke transferred through HEMS and ground-based transportation. There were no significant differences between the groups regarding the therapy administered (thrombolysis or endovascular). The studies were international, spanning multiple continents and countries including several in the United States (Conroy, PA; Olson, MN; Lukovits, NH; Almallouhi, SC; and GA), 2 from Denmark (Hesselfeldt and Funder), 1 from Japan (Ueno), and 1 from Austria (Reiner). Despite being in very different geographic locations, all of these studies had a similar distance and time for helicopter and ground transport. Despite the similarities, some studies found significant differences in the travel time between the 2 transport groups (ie, shorter and longer depending on the location and referral biases of the dispatch center).
      Table 1Characteristics of included studies.
      StudyTypePatientsOutcomeLength FollowingNOS
      Conroy et al 1999Retrospective case seriesN = 73

      Helicopter (n = 45)

      Ground (n = 28)
      Disposition

      In-hospital mortality

      Change in NIHSS at discharge
      Discharge6
      Olson et al 2012Retrospective observational CohortN = 122

      Helicopter (n = 94)

      Ground (n = 28)
      LOS

      mRS score at discharge

      30 day mortality

      Discharge

      30 days
      5
      Reiner-Deitemy er et al 2011Multicenter Prospective data collection and prespecified evaluation of dataN = 21712

      HEMS total (n = 905)

      HEMS direct (n = 752)

      HEMS indirect (n = 153)

      AMBP direct (n = 5891)

      AMBP indirect (n = 1109)

      AMB direct (n = 11357)

      AMB indirect (n = 2450)
      Rate of thrombolysis

      In-hospital6
      Lukovits et al 2013Retrospective chart reviewN = 347

      HEMS 2003-2005 (140)

      HEMS 2006-2008 (207)
      LOS

      In-hospital mortality
      Discharge5
      Hesselfeldt et al 2015Prospective controlled observational studyN = 330

      Helicopter (n = 65)

      Ground (n = 265)
      LOS

      In-hospital, 30-day, and 1-year mortality

      mRS at 3 months
      Discharge

      30 days

      3 months

      1 year
      5
      Funder et al 2017Prospective observational studyN = 1068

      Helicopter (n = 152)

      Ground (n = 916)
      LOS

      In-hospital, 30-day, and 1-year mortality

      mRS at 3 months
      Discharge

      30 days

      3 months

      1 year
      5
      Almallouhi et al 2019Retrospective chart reviewN = 199

      Helicopter(n = 100)

      Ground (n = 99)
      LOS

      90-day mortality

      90-day mRS
      Discharge

      90 days
      6
      Ueno et al 2019Retrospective observational CohortN = 546

      Helicopter (n = 61)

      Ground (n = 485)
      LOS

      30-day mortality

      mRS on discharge to home from hospital or rehab
      Discharge

      30 days

      up to 2 months
      7
      HEMS, Helicopter emergency medical service; AMB, Ambulance; AMBP, ambulance accompanied by an emergency physician; NIHSS, National Institutes of Health Stroke Scale; LOS, Length of stay; mRS, modified Rankin Scale.

      Meta-Analysis

      Mortality

      From 7 studies, the total number of cases included for mortality was 99 for helicopter transportation and 204 for emergency standard transportation (Fig. 2). Ueno et al
      • Ueno T
      • Nishijima H
      • Hikichi H
      • et al.
      Helicopter transport for patients with cerebral infarction in rural Japan.
      reported a 19.6% mortality rate in the helicopter transport group, which is the highest percentage among studies in this group (OR = 2.1; 95% confidence interval [CI], 1.09-4.38). On the other hand, Hesselfeldt et al
      • Hesselfeldt R
      • Gyllenborg J
      • Steinmetz J
      • Do HQ
      • Hejselbaek J
      • Rasmussen LS.
      Is air transport of stroke patients faster than ground transport? A prospective controlled observational study.
      noted no mortality in the helicopter transportation group. Lukovits et al
      • Lukovits TG
      • Von Iderstine SL
      • Brozen R
      • Pippy M
      • Goddeau RP
      • McDermott ML.
      Interhospital helicopter transport for stroke.
      reported the highest mortality percentage (29.2%) in the emergency standard transportation group. The pooled mortality rate in all the studies in the HEMS group was 14.5% and 11.4% in the emergency standard transportation group. This outcome was not statistically significant (OR = 0.7; 95% CI, 0.60-1.06; P = .12); however, the degree of heterogeneity was less in comparison to the reporting of a good or poor neurologic outcome (I2 = 56.25%, P = .03) (Supplemental Table 2).
      Figure 2
      Figure 2A forest plot showing mortality on HEMS in patients with stroke.

      Good Functional and Neurologic Outcome

      From 7 studies, the total number included for the good outcome assessment was 1,372 for HEMS and 8,587 for emergency standard transportation (N = 8,587) (Fig. 3). Hesselfeldt et al
      • Hesselfeldt R
      • Gyllenborg J
      • Steinmetz J
      • Do HQ
      • Hejselbaek J
      • Rasmussen LS.
      Is air transport of stroke patients faster than ground transport? A prospective controlled observational study.
      reported the highest percentage (59%) of good neurologic outcomes in the HEMS group followed by Olson et al
      • Olson MD
      • Rabinstein AA.
      Does helicopter emergency medical service transfer offer benefit to patients with stroke?.
      (58%) and Conroy et al
      • Conroy MB
      • Rodriguez SU
      • Kimmel SE
      • Kasner SE.
      Helicopter transfer offers a potential benefit to patients with acute stroke.
      (48.8%). Moreover, Olson et al
      • Olson MD
      • Rabinstein AA.
      Does helicopter emergency medical service transfer offer benefit to patients with stroke?.
      reported the highest risk (4.2-fold higher) for a good neurologic outcome, and Ueno et al
      • Ueno T
      • Nishijima H
      • Hikichi H
      • et al.
      Helicopter transport for patients with cerebral infarction in rural Japan.
      reported the lowest risk (40% lower) for a good neurologic outcome, which denotes unfavorable neurologic outcomes (given that the OR is < 1). The meta-analysis pooling all studies showed 34% good neurologic outcome in the helicopter transportation group compared with 17.5% in emergency standard transportation. The analysis showed a significant association between HEMS and good neurologic outcomes (OR = 2; 95% CI, 1.79-2.34; P ≤ .001). The degree of heterogeneity for reporting the good outcome was high (I2 =91.70%, P ≤ .0001) (Supplemental Table 3).
      Figure 3
      Figure 3A forest plot showing good neurologic and functional outcomes on HEMS in patients with ischemic stroke.

      Poor Functional and Neurologic Outcome

      For the poor functional outcome assessment, the total number included was the same as a good functional outcome assessment (Fig. 4). To highlight, Ueno et al
      • Ueno T
      • Nishijima H
      • Hikichi H
      • et al.
      Helicopter transport for patients with cerebral infarction in rural Japan.
      showed the highest percentage of poor neurologic outcomes (50.8%) followed by Funder et al
      • Funder KS
      • Rasmussen LS
      • Lohse N
      • et al.
      The impact of a physician-staffed helicopter on outcome in patients admitted to a stroke unit: a prospective observational study.
      (48%) in the HEMS group. On the other hand, Almallouhi et al
      • Almallouhi E
      • Al Kasab S
      • Nahhas M
      • et al.
      Outcomes of interfacility helicopter transportation in acute stroke care.
      noted the highest (60.6%) poor neurologic outcomes in the emergency standard transportation group. Moreover, Funder et al
      • Funder KS
      • Rasmussen LS
      • Lohse N
      • et al.
      The impact of a physician-staffed helicopter on outcome in patients admitted to a stroke unit: a prospective observational study.
      reported the highest OR (1.33) for poor neurologic outcomes. They included 152 helicopter transportation and 916 cases of emergency standard transportation. A total of 74 cases had a bad outcome in the HEMS group. The overall poor neurologic outcome was reduced in the HEMS group (OR = 0.52; 95% CI, 0.46-0.60; P ≤ .001). The overall poor outcome in the HEMS group (27.6%) was much lower compared with emergency standard transportation (42.8%). The degree of heterogeneity was similar to good functional outcome prediction (I2 = 87.03%, P ≤ .0001) (Supplemental Table 4).
      Figure 4
      Figure 4A forest plot showing poor neurologic and functional outcomes on HEMS in patients with ischemic stroke.

      Study Quality

      One study that scored 7 and 3 studies that scored 6 were considered of high methodological quality. Three studies with a score of 5 and another study with a score of 4 were considered of moderate methodological quality (Table 2).
      Table 2Newcastle–Ottawa Scale for quality assessment of studies included in this meta-analysis.
      StudyRepresentativeness of SampleSize SampleSource of informationDemonstration that outcome was not present at study startConfusion variable controlAssessment of outcomeEnough follow-upperiod
      Conroy et al 1999
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Olson et al 2012
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Reiner-Deitemyer et al 2011
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Lukovits et al 2013
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Hesselfeldt et al 2015
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Funder et al 2017
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Almallouhi et al 2019
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Ueno et al 2019
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      Indicates that it meets criteria in Newcastle–Ottawa Scale.
      low asterisk Indicates that it meets criteria in Newcastle–Ottawa Scale.

      Publication Bias

      The funnel plot shows gross asymmetry in reporting good neurologic outcomes (Fig. 5). The funnel plots for poor neurologic outcomes and mortality also showed asymmetry, but it is less compared with the reporting for good neurologic outcomes. Because there is a high degree of asymmetry, we cannot conclude that there is no publication bias. However, there are only a few studies included (< 10) with considerable heterogeneity, which could decrease the accuracy of this analysis.
      Figure 5
      Figure 5Funnel plots assessing the risk of publication bias in the studies included in the meta-analysis for different outcomes: (a) mortality, (b) poor neurologic and functional outcomes (it shows great asymmetry), and (c) good neurologic and functional outcomes.

      Discussion

      Our meta-analysis showed that the HEMS group showed reduced poor neurologic outcomes, although reduced overall mortality and a considerably better neurologic outcome were not demonstrated in patients with stroke. The positive benefits in this study may be secondary to the interplay of multispectral factors governing the HEMS, such as budget, population amount, logistic issues, supply/demand ratio, etc. Regarding demand, HEMS provides acute stroke care to 20% of the US population with an estimated 16,000 stroke helicopter missions.
      • Leira EC
      • Stilley JD
      • Schnell T
      • Audebert HJ
      • Adams HP.
      Helicopter transportation in the era of thrombectomy: the next frontier for acute stroke treatment and research.
      Most of the neurologic cases were air-transferred compromised stroke cases. This reflects the value of the adage “time is brain,” which connotes the need for expedited transfer of the justified patients by HEMS, to potentially maximize therapeutic benefits.
      • Leira EC
      • Stilley JD
      • Schnell T
      • Audebert HJ
      • Adams HP.
      Helicopter transportation in the era of thrombectomy: the next frontier for acute stroke treatment and research.
      The shortest arrival times and highest subsequent thrombolysis rates were noted among patients transported by helicopter.

      Reiner-Deitemyer V, Teuschl Y, Matz K, et al. Helicopter transport of stroke patients and its influence on thrombolysis rates: data from the Austrian Stroke Unit Registry. Stroke.2011;42:1295-1300.

      The hallmark of the treatment of stroke is timely intravenous thrombolysis, which can be governed through the telemedicine approach. However, the occasional need for bridging thrombectomy cannot be procured by the same because of the need for multidisciplinary care and the stringent management it requires.
      • Leira EC
      • Stilley JD
      • Schnell T
      • Audebert HJ
      • Adams HP.
      Helicopter transportation in the era of thrombectomy: the next frontier for acute stroke treatment and research.
      This is the rationale of the drip and ship approach, which is safe and feasible. With the reappraisal of mechanical thrombectomy as the new standard of care in stroke care and its exclusivity only in dedicated units (eg, stroke units), it has become mandatory to have a quick transport system to impact mortality and neurologic outcomes more efficiently. Our study adds value to HEMS in stroke care, and there will surely be an upsurge in HEMS in upcoming days.
      • Leira EC
      • Stilley JD
      • Schnell T
      • Audebert HJ
      • Adams HP.
      Helicopter transportation in the era of thrombectomy: the next frontier for acute stroke treatment and research.
      A helicopter transfer can be a boon in bridging remote regions to a stroke center for timely and effective thrombolytic therapy.

      Reiner-Deitemyer V, Teuschl Y, Matz K, et al. Helicopter transport of stroke patients and its influence on thrombolysis rates: data from the Austrian Stroke Unit Registry. Stroke.2011;42:1295-1300.

      From previous studies, we know that computed tomographic imaging integrated into stroke ambulances may not be a valid solution for rural settings.
      • Leira EC
      • Stilley JD
      • Schnell T
      • Audebert HJ
      • Adams HP.
      Helicopter transportation in the era of thrombectomy: the next frontier for acute stroke treatment and research.
      Moreover, ambulances have a comparative speed limit and can also be hindered by traffic congestion, road conditions, and inclement weather.
      • Conroy MB
      • Rodriguez SU
      • Kimmel SE
      • Kasner SE.
      Helicopter transfer offers a potential benefit to patients with acute stroke.
      The study of interhospital transports from Germany showed the benefits of a shorter transfer time with more than 50 km only; therefore, savings by HEMS can only be expected in settings with long distances from the scene to the hospital. The favorable results observed among the patients transferred from islands (with a median distance of 112 km) were comparable to those noted in the mainland groups in 1 study conducted in Japan.
      • Hiu T
      • Ozono K
      • Kawahara I
      • et al.
      Efficacy of the drip and ship method in 24-h helicopter transportation and teleradiology for isolated islands.
      Early arrivals and maximum thrombolysis were higher for HEMS (24% direct and 29% indirect) transfers compared with physician-accompanied ambulance transfers (18% direct and 15% indirect).

      Reiner-Deitemyer V, Teuschl Y, Matz K, et al. Helicopter transport of stroke patients and its influence on thrombolysis rates: data from the Austrian Stroke Unit Registry. Stroke.2011;42:1295-1300.

      The high initial costs of HEMS will appear nominal compared with the significant costs it saves that could have procured during rehabilitation and prolonged nursing care among stroke survivors with significant neurologic deficits.

      Reiner-Deitemyer V, Teuschl Y, Matz K, et al. Helicopter transport of stroke patients and its influence on thrombolysis rates: data from the Austrian Stroke Unit Registry. Stroke.2011;42:1295-1300.

      Regarding safety and logistics, HEMS are relatively safe.
      • Hiu T
      • Ozono K
      • Kawahara I
      • et al.
      Efficacy of the drip and ship method in 24-h helicopter transportation and teleradiology for isolated islands.
      Efficient and timely advanced life support care is 1 of the prime advantages, especially in rural setups. On the other hand, the critical care capabilities of HEMS far surpass those in the ground emergency medical services (eg, ambulance or physician-accompanied ambulance transfers). For example, airway management and resuscitation have been demonstrated superior performance and better outcomes in HEMS.
      • Hiu T
      • Ozono K
      • Kawahara I
      • et al.
      Efficacy of the drip and ship method in 24-h helicopter transportation and teleradiology for isolated islands.
      Moreover, errors relating to airway management (eg, esophageal intubations, inadvertent weaning, etc) are more common in in-ground transports.
      • Hiu T
      • Ozono K
      • Kawahara I
      • et al.
      Efficacy of the drip and ship method in 24-h helicopter transportation and teleradiology for isolated islands.
      The effective prehospital management of HEMS crews and efforts on these patients overshadow the nominal prehospital delay compared with road transports.
      • Hiu T
      • Ozono K
      • Kawahara I
      • et al.
      Efficacy of the drip and ship method in 24-h helicopter transportation and teleradiology for isolated islands.
      HEMS teams are more capable of making correct therapeutic judgments and needful management procedures compared with their ambulance counterparts.
      • Hiu T
      • Ozono K
      • Kawahara I
      • et al.
      Efficacy of the drip and ship method in 24-h helicopter transportation and teleradiology for isolated islands.
      HEMS can aid in neuroprotective and reperfusion-mitigating measures during the transfer that potentially compensate for this delay.
      • Leira EC
      • Stilley JD
      • Schnell T
      • Audebert HJ
      • Adams HP.
      Helicopter transportation in the era of thrombectomy: the next frontier for acute stroke treatment and research.
      HEMS teams can also facilitate the informed consent process by up to almost 70%, which is very commendable in such a time-pressured medical process.
      • Leira EC
      • Stilley JD
      • Schnell T
      • Audebert HJ
      • Adams HP.
      Helicopter transportation in the era of thrombectomy: the next frontier for acute stroke treatment and research.
      Helicopter transfer has also been shown to be highly effective in other domains of good clinical outcome such as quality-adjusted life years.
      • Silbergleit R
      • Scott PA
      • Lowell MJ
      • Silbergleit R.
      Cost-effectiveness of helicopter transport of stroke patients for thrombolysis.
      Regarding patient selection and financial issues, HEMS are 5 times more expensive ($6,000-$25,000 per activation) compared with ground ambulance services ($1,200-$4,000 per activation).
      • Elvik R.
      Cost-benefit analysis of ambulance and rescue helicopters in Norway: reflections on assigning a monetary value to saving a human life.
      ,
      • Kashyap R
      • Anderson PW
      • Vakil A
      • Russi CS
      Cartin-Ceba R. A retrospective comparison of helicopter transport versus ground transport in patients with severe sepsis and septic shock.
      In 1 study from Norway comprising 370 patients, only 11.1% of transfers were considered to have benefited from the airlift.
      • Hotvedt R
      • Thoner J
      • Almdahl SM
      • et al.
      Which groups of patients benefit from helicopter evacuation?.
      Undertriage even at the range of 5% to 10% is to be prevented.
      • Thomas SH
      • Brown KM
      • Oliver ZJ
      • et al.
      An evidence-based guideline for the air medical transportation of prehospital trauma patients.
      Undertriage can seriously jeopardize the timely implementation of therapeutic intervention, whereas overtriaging can hamper the dichotomous implementation of health resources following overutilization, especially in developing nations
      • Thomas SH
      • Brown KM
      • Oliver ZJ
      • et al.
      An evidence-based guideline for the air medical transportation of prehospital trauma patients.
      ; the preselection of ischemic stroke patients requiring thrombolysis; and the judicious assignment of their mode of transfer to the dedicated center.

      Reiner-Deitemyer V, Teuschl Y, Matz K, et al. Helicopter transport of stroke patients and its influence on thrombolysis rates: data from the Austrian Stroke Unit Registry. Stroke.2011;42:1295-1300.

      Telemedicine may be 1 strategy for improving air transport triage.

      Reiner-Deitemyer V, Teuschl Y, Matz K, et al. Helicopter transport of stroke patients and its influence on thrombolysis rates: data from the Austrian Stroke Unit Registry. Stroke.2011;42:1295-1300.

      HEMS transfer of the interventionist can be a more economical and rational alternative to the existing spoke-and-hub model of stroke management.
      • Hui FK
      • El Mekabaty A
      • Schultz J
      • et al.
      Helistroke: neurointerventionalist helicopter transport for interventional stroke treatment: proof of concept and rationale.
      This has shown favorable results in terms of the reduced door to puncture time with added benefits of simplifying the management algorithm along with safeguarding the patient from the risks associated with air transfer.
      • Hui FK
      • El Mekabaty A
      • Schultz J
      • et al.
      Helistroke: neurointerventionalist helicopter transport for interventional stroke treatment: proof of concept and rationale.
      Studies have shown no significant differences in mortality and functional outcome among patients transferred by HEMS compared with ambulance transport.
      • Olson MD
      • Rabinstein AA.
      Does helicopter emergency medical service transfer offer benefit to patients with stroke?.
      Patients in the HEMS group showed higher National Institute of Health Stroke Scale scores and were neurologically more unstable, which would have skewed the better outcome among patients transported by ground emergency medical services.
      • Ueno T
      • Nishijima H
      • Hikichi H
      • et al.
      Helicopter transport for patients with cerebral infarction in rural Japan.
      HEMS patients also were transferred from a more distant catchment area. Studies also have shown a relatively longer time lapse between the initial triage to the arrival to the referred center in HEMS patients.
      • Funder KS
      • Rasmussen LS
      • Lohse N
      • et al.
      The impact of a physician-staffed helicopter on outcome in patients admitted to a stroke unit: a prospective observational study.
      The dispatch is done after stabilization of the sick patient and secondary to a ground unit on-site, thus accounting for such a delay.
      • Funder KS
      • Rasmussen LS
      • Lohse N
      • et al.
      The impact of a physician-staffed helicopter on outcome in patients admitted to a stroke unit: a prospective observational study.
      A higher degree of stabilization of critical patients before transport is needed. Transport times for either air or ground emergency medical services are mostly estimated retrospectively (ie, lacking information about traffic or weather conditions), further diluting the validity of these results.
      • Hiu T
      • Ozono K
      • Kawahara I
      • et al.
      Efficacy of the drip and ship method in 24-h helicopter transportation and teleradiology for isolated islands.
      Activation times, response times, on-scene times, ground dispatch times, and “setup” times are shorter for ground transportation because of the short distance to be covered and because patients are comparatively more stable than their HEMS counterparts.
      • Funder KS
      • Rasmussen LS
      • Lohse N
      • et al.
      The impact of a physician-staffed helicopter on outcome in patients admitted to a stroke unit: a prospective observational study.
      ,
      • Nicholl JP
      • Beeby NR
      • Brazier JE.
      A comparison of the costs and performance of an emergency helicopter and land ambulances in a rural area.
      ,
      • Svenson JE
      • O'Connor JE
      • Lindsay MB.
      Is air transport faster? A comparison of air versus ground transport times for interfacility transfers in a regional referral system.
      The studies have the inherent bias of their retrospective pattern of studies, with no proper documentation of the patient dispatch time, ground transport time, and the overall out-of-hospital time lapse for authentic comparisons. Most of the studies that did not find a clear advantage of HEMS had a facility transfer distance of less than 1 hour duration.
      • Svenson JE
      • O'Connor JE
      • Lindsay MB.
      Is air transport faster? A comparison of air versus ground transport times for interfacility transfers in a regional referral system.
      The net transport times are comparable for helicopter transport and direct ambulance transport facilitated with the provision of an emergency physician. It may not be cost-effective to engage a physician in the flight rescues.
      • Dalton AM
      • Botha A
      • Coats T
      • et al.
      Helicopter doctors?.
      • Gurland BH
      • Asensio JA
      • Kerstein MD.
      A more cost-effective use of medical air evacuation personnel.
      • Rhee KJ
      • Strozeski M
      • Burney RE
      • Mackenzie JR
      LaGreca-Reibling K. Is the flight physician needed for helicopter emergency medical services?.
      Air medical transport can have adverse events relating to communication errors and equipment failures occurring as high as 30%.
      • Hui FK
      • El Mekabaty A
      • Schultz J
      • et al.
      Helistroke: neurointerventionalist helicopter transport for interventional stroke treatment: proof of concept and rationale.
      As previously reported, transfer efficacy depends on logistics before emergency medical services arrival and the speed of travel
      • Kunte SA
      • Anderson D
      • Brown-Espaillat K
      • Froehler MT.
      Total trans2fer time for ground vs. air transport for interhospital and scene transfers of acute stroke patients.
      ; therefore, not only the availability of HEMS but also a high-standard strategy for operative logistics need to be carried out. Challenges that the staff has to surpass include a lack of recognition of the importance of logistics, a lack of professional staff, inadequate use of technology, a lack of institutional learning, and limited collaboration.
      • Thomas AS
      • Kopczak LR.
      These could determine the outcome in patients with ischemic stroke in settings with HEMS availability. From the logistics insight, it is possible to take the results from a hierarchical analysis developed in the context of helicopter transportation for humanitarian aid purposes and rescues (eg, natural disasters). When adopted, this system involves a 4-phase protocol: 1) determining the most available and effective helicopter source, 2) assignment of trained pilots (including trained physicians), 3) determining a strategic route to reach the best center to match with the patients’ needs, and 4) the staff at the stroke care unit prepared to admit the patient.
      • Barbarosoğlu G
      • Özdamar L
      • Çevik A.
      An interactive approach for hierarchical analysis of helicopter logistics in disaster relief operations.
      The lack of an imaging facility is a limiting factor. Transcranial Doppler imaging, although portable, cannot rule out hemorrhages to facilitate early thrombolysis during direct transfers.
      • Leira EC
      • Stilley JD
      • Schnell T
      • Audebert HJ
      • Adams HP.
      Helicopter transportation in the era of thrombectomy: the next frontier for acute stroke treatment and research.
      There are technical limitations in installing a computed tomographic device on board, which would increase the weight of the helicopter and thereby the consumption of more fuel on a long-distance rescue.
      • Leira EC
      • Stilley JD
      • Schnell T
      • Audebert HJ
      • Adams HP.
      Helicopter transportation in the era of thrombectomy: the next frontier for acute stroke treatment and research.
      There is also the need for separate helipads. Factors such as vibration, loud noise, accelerations, alteration in barometric pressure, and partial pressure of oxygen can alter the milieu of the ischemic core and the surrounding zone of the penumbra.
      • Leira EC
      • Stilley JD
      • Schnell T
      • Audebert HJ
      • Adams HP.
      Helicopter transportation in the era of thrombectomy: the next frontier for acute stroke treatment and research.
      The hypobaric environment can have a deleterious effect on the penumbral zone.
      • Leira EC
      • Stilley JD
      • Schnell T
      • Audebert HJ
      • Adams HP.
      Helicopter transportation in the era of thrombectomy: the next frontier for acute stroke treatment and research.
      Sudden changes in speed and loud noise can aggravate nausea and vomiting, thereby worsening intracranial pressure. Paradoxically, low-frequency vibrations can have a synergistic effect to boost the effect of thrombolysis.
      • Leira EC
      • Stilley JD
      • Schnell T
      • Audebert HJ
      • Adams HP.
      Helicopter transportation in the era of thrombectomy: the next frontier for acute stroke treatment and research.
      Functional survival benefits accrued by HEMS must always outweigh the risks and safety issues relating to air transport. Field triage and helicopter dispatch criteria must be implemented and regularly audited for the refinement of protocols for mitigating unneeded transfers, containment of health costs, and ensuring safety.
      • Cameron PA
      • Flett K
      • Kaan E
      • Atkin C
      • Dziukas L.
      Helicopter retrieval of primary trauma patients by a paramedic helicopter service.
      ,
      • Ashkenazi I
      • Zeina AR
      • Kessel B
      • et al.
      Effect of teleradiology upon pattern of transfer of head injured patients from a rural general hospital to a neurosurgical referral centre: follow-up study.
      ,
      • Norton R
      • Wortman E
      • Eastes L
      • Daya M
      • Hedges J
      • Hoyt J.
      Appropriate helicopter transport of urban trauma patients.
      HEMS services do not confer benefits to patients who were transferred after thrombolysis compared with ground ambulance transport.
      • Olson MD
      • Rabinstein AA.
      Does helicopter emergency medical service transfer offer benefit to patients with stroke?.
      Ground transport should be considered unless there is a consideration for endovascular rescue therapy in the patient and clinical benefit to the patient.
      • Thomas SH
      • Brown KM
      • Oliver ZJ
      • et al.
      An evidence-based guideline for the air medical transportation of prehospital trauma patients.
      ,
      • Olson MD
      • Rabinstein AA.
      Does helicopter emergency medical service transfer offer benefit to patients with stroke?.
      ,
      • Hui FK
      • El Mekabaty A
      • Schultz J
      • et al.
      Helistroke: neurointerventionalist helicopter transport for interventional stroke treatment: proof of concept and rationale.

      Limitations

      The main limitation of our study is the sample size of the relevant studies about the role of HEMS in improving neurologic outcomes and mortality among stroke patients. Most of the studies were retrospective. Therefore, the transit delay, cause of the delay, nature of the weather, and the status of the congestion cannot be recalled exactly to frame a true comparative analysis with the road transfer. Most of the studies also did not take into account these relevant variables, which are cornerstones in modifying the outcomes in such studies. Therefore, it is justifiable to conduct multicentric prospective comparative studies, governing multispectral domains of the outcome, among such study cohorts. Also, all studies were nonrandomized observational cohort studies. The most common limitations or potential biases reported were small sample sizes and a lack of control over which patients were selected by the dispatch center for air transport as well as a lack of data on patients who were not transported by ground or air and instead remained at the originating hospital for care. Heterogeneity in this group of 8 studies is high for a meta-analysis and ranges by outcome studied from 56% to 92% in our 3 outcome categories. There are clinical or methodological differences between studies, and the variety of study sites and population sizes contributes to the heterogeneity. For example, Reiner-Deitemyer et al

      Reiner-Deitemyer V, Teuschl Y, Matz K, et al. Helicopter transport of stroke patients and its influence on thrombolysis rates: data from the Austrian Stroke Unit Registry. Stroke.2011;42:1295-1300.

      added about 70% of patients in the meta-analysis of neurologic outcome but not in mortality, which means that this study vastly influenced the heterogeneity of the neurologic outcome of our analysis. Therefore, further studies should be conducted including larger samples to better elucidate the true role of HEMS in patients diagnosed with acute stroke. There are also other factors noted in the previously described analysis. There were 3 prospective studies and 5 retrospective studies. The inclusion criteria were mostly similar, with the notable exceptions of thrombolysis before transport, suspicion for large vessel occlusion before transport, and inclusion of hemorrhagic stroke patients (which was minimal and exclusively 1 study). It needs to be highlighted that the functional outcome could be influenced by thrombolysis because it is 1 of the most important determinants of outcomes; however, as mentioned earlier, HEMS increases the chance of receiving both thrombolysis and endovascular treatment. One important limitation of our study is the lack of discrimination of the impact of each measure separately in the care of patients with ischemic stroke. One study also lacked a ground transport control group and, instead, they compared two groups of helicopter transport patients during two consecutive time frames of 3-year. The baseline matching of prognostic criteria in the patients transported and the control stroke patients not transported by helicopter could probably entail selection criteria and selection bias. Moreover, outcome units could be an issue because some outcomes were reported in National Institute of Health Stroke Scale changes, whereas others were reported by GOS or mRS. More than the difference in units, the outcome timeline varied significantly between studies, with 3 of 8 studies only reporting mortality or functional outcome at the time of discharge and 2 studies reporting functional outcome or mortality only at discharge and 30 days. The location varied, with several in the United States, 2 from Denmark, 1 from Japan, and 1 from Austria. It is hard to assess the degree to which such geographic differences or local cultural differences in patient populations contribute to heterogeneity, but it is impossible to rule out such effects. Besides differences in a physical locale, the quality of roads and the quality of ground transport services may affect the patients’ distribution into air and ground transport groups.

      Conclusion

      Poor neurologic outcomes were reduced in the HEMS group compared with the emergency standard transportation group. No differences were found in mortality and a good neurologic outcome between the HEMS and emergency standard transportation groups after pooled analysis. The degree of heterogeneity was high in reporting the good and poor neurologic outcomes; therefore, larger randomized controlled studies are needed to reduce heterogeneity. Moreover, a multidisciplinary approach is needed to better implement HEMS and achieve a huge impact on outcomes.

      Appendix. Supplementary materials

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