The impact of delivery by a fixed-wing, sling-launched unmanned aerial vehicle on the hematologic function of whole blood

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BACKGROUND

Unmanned aerial vehicles (UAVs) have been shown to shorten delivery times of medical products in health care, providing a potential answer to the question of prehospital resuscitation where blood and blood products are not readily available. While the capabilities and efficiencies of delivery via UAVs are already well established, the postdelivery viability and hemostatic function of whole blood has not been examined.

METHODS

Whole blood units were sampled for a preflight control and loaded onto a fixed wing UAV. The UAVs flew in predetermined flight paths to either deliver via parachute drop or direct recovery after UAV capture by arresting gear. Postflight and preflight samples were assayed for coagulation function with thromboelastography, blood chemistry, and free hemoglobin to observe hemolysis.

RESULTS

No significant differences in any metric were observed between the blood samples assayed preflight versus those flown and parachute dropped or those flown and recovered from the UAV.

CONCLUSION

The use of UAVs for delivery of whole blood offers significant benefits for prehospital care. Further innovations in UAV and transportation technologies will expand on an already strong foundation.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level IV.

Prehospital resuscitation with whole blood is critical in combating morbidity and mortality associated with hemorrhagic shock.^1–4 The military has made great effort to provide early resuscitation with the golden hour,^5,6 low titer group O whole blood (LTOWB),^7,8 and “walking blood bank”/“buddy transfusion” programs.^9–12 Unfortunately, blood still remains scarce in the prehospital setting due primarily to the logistics involved in distribution and delivery to the site of trauma coupled with its perishability. Whole blood can be kept in an insulated container for short periods, but longer durations outside of proper refrigeration storage typically means temperature excursions resulting in nonviability of the product. Thus, blood can be difficult to maintain in supply, and having the capacity for rapid delivery, has become a goal for far forward transfusion.

Unmanned aerial vehicles (UAVs) have the benefit of being small and fast and are unaffected by terrain to deliver payloads. Unmanned aerial vehicles are starting to be used for delivery in health care, including COVID-19 samples in Ghana and emergency blood delivery in Canada.^13–15 Zipline, a logistics company specializing in autonomous delivery systems, designs, manufacturers, and operates its P1 fixed-wing UAV delivery craft that utilizes a launching platform to quickly deploy at speed, with autonomous flight and precision delivery, providing 850 to 1,250 medical shipments per day globally in several countries, including Ghana, Nigeria, Côte d’Ivoire, Japan, and the United States. In addition, the government of Rwanda has contracted Zipline for UAV blood delivery, making up to 500 trips per day by parachute drop.¹⁶ This collaboration led to a 71% reduction in median delivery time compared with road-based parcels and ultimately led to a 67% decrease in waste-based product expiration.

Unmanned aerial vehicles for delivery in health care have been evaluated for time, efficiency, economics, and storage conditions,^17,18 but not for their ability to maintain whole blood functionality and viability. Zipline utilizes a catapulting launching platform, a parachute delivery system, and an arresting apparatus to recover UAVs mid-flight. Each of these could potentially impact the biological viability of the cargo. A previous study examined the effects of parachute dropping blood in various configurations, finding no significant deviations between dropped and control undropped blood,¹⁹ but this study was conducted to evaluate the hypothesis that the health and hemostatic function of whole blood units would be affected by being subjected to the specific stresses of a Zipline UAV launch, flight, and recovery, with primary outcomes being hemolysis as measured by free hemoglobin and coagulation function as measured by TEG. We hypothesized that the stresses of the delivery process would induce hemolysis.

METHODS

Units of near expiration (18–21 days old) deidentified, non-leukoreduced, LTOWB (n = 30) were provided by Armed Services Whole Blood Processing Laboratory-East. Blood units were each spiked with a Luer lock transfer pin (Fresenius Kabi, Lake Zurich, IL), and a preflight sample was taken for reference. Samples were packaged and flown via Zipline (San Francisco, CA) on their fixed-wing UAV with autonomous flight on pre-programed paths (Fig. 1) for durations of 3 minutes to 7 minutes at a Zipline testing site in Yolo Co., California. All flights were conducted on a single summer day with ambient temperatures above 100°F. Individual units were rolled in bubble wrap and packing paper before being loaded into the cargo container (2 units per box) which was placed into the UAV's payload compartment. The UAV was launched from a high acceleration sling, and, under multiple flight paths, whole blood cargo was delivered via parachute drop prior to UAV recovery with an arresting wire. Units taken on flights with longer flight paths (7 minutes) and delivered from 100 m altitude are labeled as “long,” whereas units taken on flights with shorter flight paths (3 minutes) and delivered from 25 m altitude are labeled as “short.” Finally, units that did not drop but were recovered from the UAV's payload after the flight had completed (8–20 minutes) are labeled as “recovered” to investigate the impact of the rapid deceleration provided by the arresting wire. Maximum altitude during flight was 900 ft above ground level, and maximum air speed was 61 miles per hour.

Figure 1.

The “close delivery route” had a flight duration of 3 minutes with cargo deployment from an altitude of 25 m. The “far delivery route” had a flight duration of 7 minutes with cargo deployed from an altitude of 100 m.

Whole blood samples' coagulation functions were assayed with RapidTEG on a TEG 6s (Haemonetics, Boston, MA), and blood chemistry measurements were taken with CG4+ cartridges on i-STAT (Abbott Point of Care, Princeton, NJ). Remaining sample was centrifuged at 2,500g for 15 minutes to isolate platelet-poor plasma to assay free hemoglobin on a Hemocue Plasma/Low Hb System (Hemocue, Brea, CA). The viability of a sample was gauged through changes in free hemoglobin (HGB) as a measure of hemolysis, partial pressure of oxygen (pO₂), and lactate levels.

Data were analyzed in GraphPad Prism 9 (GraphPad, San Diego, CA). One-way ANOVA with repeated measures was performed to determine differences between the three groups: Control, Dropped, and Recovered. Paired t tests were performed to determine differences between flown samples and the controls. Data are reported as box and whisker plots with medians and min-to-max whiskers, and the box representing lower and upper quartiles.

RESULTS

Each unit of whole blood was sampled for baseline control, then subsequently packed and flown on a Zipline UAV. Samples were either dropped via parachute deployment mid-flight (n = 22) or recovered with the UAV after being caught on with an arresting wire with a tailhook (n = 8). UAV flights were set on either a short (n = 18) or long path (n = 4). Since no statistical differences were observed between dropped samples on the long or short flight path, the data from both short and long flight samples were combined categorically as “Dropped” samples for analysis purposes.

There was no statistical difference between control, dropped, and recovered samples when probing HGB, with averages of 59.67 ± 25.8 mg/dL, 60.91 ± 35.31 mg/dL, and 60 ± 28.28 mg/dL, respectively (Fig. 2). The mean of differences for the recovered samples was 5 ± 17.73 mg/dL. The pO₂ was 33.47 ± 5.746 mm Hg for the control, 34.38 ± 6.352 mm Hg for dropped, and 33.5 ± 3.207 mm Hg for recovered, with no statistical significance determined. In addition, no significance was found in lactate with 16.35 ± 1.915 mM for control, 16.8 ± 1.863 mM for dropped, and 17.07 ± 0.847 mM for recovered.

Figure 2.

Free hemoglobin (Hb), pO₂, and lactate did demonstrate any significant differences between the pre-flight control samples and either dropped or recovered samples. Data are displayed as medians inside lower-to-upper quartile box with min-to-max whiskers.

Holistic coagulability was assayed for using TEG 6s RapidTEG output (Fig. 3). The time for clot formation, measured as R-time, was 8.022 ± 0.851 minutes for control, 7.943 ± 0.922 minutes for dropped, and 7.775 ± 0.822 minutes for recovered. The rate of clot formation (alpha angle) was 58.78 ± 5.132°, 58.27 ± 5.109°, and 65.9 ± 8.728° for control, dropped, and recovered, respectively. Finally, the strength of the clot was measured as maximum amplitude, measuring at 47.88 ± 4.402 mm for control, 46.95 ± 3.56 mm for dropped, 46.9 ± 3.753 mm for recovered. No measurements for coagulability were statistically significant.

Figure 3.

No statistically significant differences were observed between preflight control samples and post flight (either parachute dropped or UAV recovered) samples on the TEG 6s. A trend for higher median for angle was noted for the recovered samples (67.2° vs. 58.55° and 59.7° for control and dropped, respectively). Data are displayed as medians inside lower-to-upper quartile box with min-to-max whiskers.

DISCUSSION

Hemorrhagic shock-associated lethality in combat zones²⁰ and the difficulty of maintaining blood products in the far forward setting combine to form a key hurdle to overcome in the effort to increase survivability of the wounded warfighter. Blood products have limited shelf lives and require specialized cold chain transport and storage which compounds to prohibit utilization in areas without facilities, utilities, and equipment to properly care for and prepare them.

Blood products carried by medics must be properly stored to maintain temperature and be protected from physical hazards to prevent rupture. In addition, medic-carried transport containers have a capacity of one or two blood units and can only maintain temperature for a very limited time, precluding extended excursions. While walking blood bank and “buddy” transfusions are proposed solutions for these problems, they come with their own sets of logistical issues. Testing, tracking, and organizing warfighters to have enough LTOWB donors dispersed among squads of soldiers is logistically complicated, and the uncertain quantity of LTOWB donors available is detrimental to wide-spread adoption of a walking blood bank. On the other hand, organizing safe blood typed buddy systems has been difficult, and medics are not yet reliably trained on conducting buddy transfusions.

Unmanned aerial vehicle delivery of blood products presents a viable solution to circumvent these issues. With location tracking, blood can be delivered with precision far faster than ground-based methods, and many UAVs are small and discrete enough to deliver packages into zones potentially too dangerous for manned-vehicle deployment. As we consider a future with multidomain operations where air superiority against peer or near-peer adversaries is not guaranteed, vehicles with stealth, speed, and sufficient payload become more attractive. This is especially true if the usage of these vehicles does not put any additional service members at risk. While only one of many potential UAV solutions, Zip line’s previous efforts in Rwanda and Ghana, and others in Canada, China, Sweden, Australia, and Malaysia have proven a marked ability to cut down on delivery times using a variety of UAVs.

This brief current study demonstrated no significant difference seen in blood viability and coagulation function predelivery and postdelivery, whether they were parachute-dropped or undelivered and recovered, showing no marked effect of take-off, parachute delivery, or recovery without delivery. Elevated lactate levels are of note compared with expected levels of fresh whole blood; however, as there is no difference between predelivery and postdelivery this is likely due to the age of the blood. This indicates no net negative effect from UAV transport on the blood as measured from these markers for flights of this duration.

This study was limited in the scope of analysis due to the in situ nature of collections from UAVs, and other factors including platelet activation and aggregation should be examined as a focus of future study but were unavailable in the small field laboratory. In addition, the study did not assess the level of environmental protection in UAVs compared with traditional transport methods. Temperatures during these short flights were unmonitored, and longer flights could have made an impact on viability through temperature excursion. However, this study was focused on the effects resulting from the launch and parachute delivery or undelivered recovery, which are unique elements to this platform and have not been previously evaluated. Considerations for the future would be, but are not limited to, temperature and pressure maintenance throughout flight through insulation and refrigeration, inclusion of a pre-warmer for the blood to be transfusion-ready upon arrival, and increased payload size beyond one or two units. Innovation in package deployment could improve reliability, as parachute failure is a concern when delivering life-saving components (although one unit was subjected to a non-parachute free fall drop from 25 m that did not cause any visible damage to the blood bags or impairment to the measured parameters). Beyond cargo, considerations for UAVs include distance and duration of flight, largely limited because of current battery technologies, stealth capabilities to ensure safe delivery into dangerous zones, speed to reduce time to arrival from request even further, and alternatives to fixed wing designs that can improve capacity and maneuverability.

Unmanned aerial vehicles like Ziplines have demonstrated the capacity to significantly improve delivery times and reduce expiration-related waste. This study has also shown that the rapid acceleration and deceleration produced by the launch and landing or recovery processes have no measured harmful effects on the viability of the product. Temperature control for cold-chain preservation and long-term flight effects (including turbulence, humidity, and pressure changes) are priorities to consider when evaluating the usefulness of UAV delivery of blood, and many manufacturers are preparing to accommodate the specific needs of blood in their designs. The incorporation of UAVs into the toolset of military operational medicine will undoubtedly be a key element as the United States moves to more hotly contested battlefields with limited access and difficult casevac/medevac.