Whole blood in prehospital damage control resuscitation : -Safety, feasibility, and logistics

Bakgrunn De siste tiårene har det vært et paradigmeskifte i behandlingen av blødningsjokk. Skadebegrensende resuscitering har som hensikt å understøtte hemostatisk evne hos pasienten og reversere og dempe konsekvensene av sjokk slik at pasienten har tilstrekkelige fysiologiske reserver til å overleve påfølgende behandling i sykehus. Strategien baserer seg i all hovedsak på å starte tidlig behandling med blod og blodprodukter. I økende grad har sivile og militære prehospitale tjenester vurdert fullblod som et alternativ for den intiale resusciteringen av blødningsjokk. Selv om fullblod har tiltalende egenskaper er det flere utfordringer ved implementering av fullblod i et prehospitalt system. Forhold knyttet til sikkerhet, logistikk, lagring og praktisk bruk bør evalueres. Mål Å undersøke og evaluere implementeringen av et program for implementering av prehospitalt lavtiter gruppe O fullblod (LTOWB). Metode Paper I undersøkte gjennomførbarhet, sikkerheten og effektivitet av intraossøs sternal autolog re-infusjon av varmt friskt fullblod (WFWB) i en prospektiv human komparativ studie. Paper II undersøkte ex vivo kvaliteten til lav titer type O fullblod (LTOWB) under fremskutt lagring i opptil 21 dager i en lufttett temperaturregulert beholder ved en luftambulansebase sammenlignet med LTOWB lagret i blodbanken. Paper III identifiserte nåværende prehospitale blodtransfusjonsprogrammer, fremtidige behov og potensielle barriærer for implementering av LTOWB i en spørreundersøkelse blant medisinsk ansvarligeleger ved luft og redningshelikoptertjenestene i Norge. Paper IV beskrev implementeringen av et LTOWB-transfusjonsprogram i Luftambulansetjenesten i Bergen i perioden 2015-2020 i en prospektiv observasjonsstudie. Resultater Det var ingen hemolyse etter sternal intraossøs re-infusjon av fullblod. Median infusjonshastighet var 46,2 ml/min for FAST-1-IO nålen, og feilraten ved innleggelse av IO tilgangen for uerfarent personell var 9 %. Fremskutt lagring av LTOWB opptil 21 dager førte ikke til konsekvenser som kan true pasientsikkerheten. Blodet tilfredstilte EU krav i hele lagringsperioden. Det var ingen signifikante forskjeller i de hematologiske variablene, blodplateaggregering eller viskoelastiske egenskaper mellom blod lagret fremskutt og blod lagret i blodbanken. Alle luft og redningshelikopter i Norge har blodprodukter tilgjengelig. Fire av 20 (20 %) har implementert LTOWB. Et flertall av tjenestene har en preferanse for LTOWB siden dette muliggjør tidlig balansert transfusjon og kan ha logistiske fordeler i tidskritiske situasjoner. Blodbanker som leverer LTOWB rapporterer gunstige erfaringer. I løpet av 2015-2020 responderte Luftambulansen i Bergen til 5124 pasienter. Syttito (1,4%) mottok blodtransfusjon. 52 pasientene samtykket til deltagelse i studien. Av disse fikk 48 LTOWB. Førtiseks (88 %) ble innlagt på sykehuset i live, og 76 % av disse fikk ytterligere transfusjoner i løpet av de første 24 timene. De fleste pasienter presenterte med stump skademekanikk (69 %), etterfulgt av blødninger som ikke var relatert til traumer (29 %). Totalt overlevde 36 (69%) 24 timer, og 28 (54%) overlevde 30 dager. Ingen transfusjonsreaksjoner eller logistiske problemer ble rapportert. Konklusjon Intraossøs infusjon av WFWB er trygt, pålitelig og gir tilstrekkelig flow for den initielle resuscitering ved blødningsjokk. Fremskutt lagring av LTOWB i Luftambulansetjenesten er gjennomførbart og trygt. Kvalitet tilfredstiller EU krav opptil 21 dagers lagring, og hemostatiske egenskaper e LTOWB sammenlingbar med LTOWB lagret i blodbanken. Luftambulansetjenestene og blodbankene som leverer LTOWB har gode erfaringer med implementering av LTOWB. Våre undersøkelser viser at implementering av et prehospitalt transfusjonsprogram med fullblod er mulig og sikkert. Det er videre behov for studier som ser på effektiviteten av fullblod sammenlignet med blodkomponenter.Background In the last two decades, resuscitation of hemorrhagic shock has undergone a paradigm shift. Modern damage control resuscitation strategies aim to improve outcomes by facilitating early hemostatic resuscitation with blood and blood products. The ultimate goal is to prevent, reverse or mitigate the severity and duration of shock and its consequences until definitive hemorrhage control can be achieved. As a result, both civilian and military EMS systems are considering whole blood for prehospital resuscitation of hemorrhagic shock. Although appealing, establishing a robust system for forward resuscitation with whole blood is challenging as several vital factors regarding safety, logistics, and implementation barriers need to be considered. Aim To investigate and evaluate the implementation of a pre-hospital low titer group O whole blood (LTOWB) transfusion program. Methods Paper I investigated the feasibility, safety, and efficacy of autologous re-infusion of warm fresh whole blood (WFWB) through an intraosseous sternal device in a prospective human comparative study. Paper II investigated the ex vivo quality of LTOWB during storage for up to 21 days in an airtight thermal container at a helicopter emergency medical system (HEMS) base compared to LTOWB stored in the blood bank. Paper III identified current pre-hospital blood transfusion programs, future needs, and potential obstacles in implementing LTOWB in a national survey among the medical directors of the Norwegian HEMS and Search and Rescue (SAR) helicopter bases. Finally, in a prospective observational study, paper IV described and evaluated the implementation of a LTOWB program in one of the Norwegian HEMS services in 2015-2020. Results There was no evidence of hemolysis following sternal intraosseous re-infusion of whole blood. The median infusion rate was 46.2mL/min for the FAST-1 device, and the failure rate for inexperienced personnel was 9%. Storage of LTOWB complied with the EU regulations throughout remote and in- hospital storage for 21 days. In addition, there were no significant differences in hematology variables, platelet aggregation, or viscoelastic properties between blood stored remotely and in the blood bank. All HEMS and SAR helicopter services in Norway carry LTOWB or blood components. A majority of services have a preference for LTOWB because LTOWB enables early balanced transfusion and may have logistical benefits in time-critical emergencies. This far, four of 20 (20%) have implemented LTOWB. Blood banks and services that provide LTOWB report favorable experiences. During the five years, the Bergen HEMS in study IV responded to 5124 patients. Seventy-two (1.4%) were transfused. Twenty patients were excluded mainly due to a lack of informed consent. Of the 52 patients, 48 received LTOWB. Forty-six (88%) were admitted to the hospital alive, and 76% of these received additional transfusions during the first 24 hours. Most patients presented with blunt trauma mechanisms (69%), followed by hemorrhage unrelated to trauma (29%). Overall 36 (69%) survived 24 hours, and 28 (54%) survived 30 days. No suspected transfusion reactions or logistical issues were reported. Conclusion WFWB transfusion through the IO route is safe, reliable, and provides sufficient flow for the initial resuscitation of hemorrhagic shock. Storage of LTOWB in thermal containers in a pre-hospital HEMS service is feasible and safe. Hemostatic properties are present for up to 21 days of storage and are similar to LTOWB stored in the blood bank. HEMS services and blood banks report favorable experiences implementing and utilizing LTOWB in Norway. The logistics of LTOWB emergency transfusions are manageable and safe in a Norwegian HEMS service.Doktorgradsavhandlin

Prehospital Whole Blood Transfusion Programs in Norway

Background: Prehospital management of severe hemorrhage has evolved significantly in Norwegian medical emergency services in the last 10 years. Treatment algorithms for severe bleeding were previously focused on restoration of the blood volume by administration of crystalloids and colloids, but now the national trauma system guidelines recommend early balanced transfusion therapy according to remote damage control resuscitation principles. Materials and Methods: This survey describes the implementation, utilization, and experience of the use of low titer group O whole blood (LTOWB) and blood components in air ambulance services in Norway. Medical directors from all air ambulance bases in Norway as well as the blood banks that support LTOWB were invited to participate. Results: Medical directors from all 13 helicopter emergency medical services (HEMS) bases, the 7 search and rescue (SAR) helicopter bases, and the 4 blood banks that support HEMS with LTOWB responded to the survey. All HEMS and SAR helicopter services carry LTOWB or blood components. Four of 20 (20%) HEMS bases have implemented LTOWB. A majority of services (18/20, 90%) have a preference for LTOWB, primarily because LTOWB enables early balanced transfusion and has logistical benefits in time-critical emergencies and during prolonged evacuations. Conclusion: HEMS services and blood banks report favorable experiences in the implementation and utilization of LTOWB. Prehospital balanced blood transfusion using whole blood is feasible in Norway.publishedVersio

Validation of a point-of-care capillary lactate measuring device (Lactate Pro 2)

Background The measurement of lactate in emergency medical services has the potential for earlier detection of shock and can be performed with a point-of-care handheld device. Validation of a point-of-care handheld device is required for prehospital implementation. Aim The primary aim was to validate the accuracy of Lactate Pro 2 in healthy volunteers and in haemodynamically compromised intensive care patients. The secondary aim was to evaluate which sample site, fingertip or earlobe, is most accurate compared to arterial lactate. Methods Arterial, venous and capillary blood samples from fingertips and earlobes were collected from intensive care patients and healthy volunteers. Arterial and venous blood lactate samples were analysed on a stationary hospital blood gas analyser (ABL800 Flex) as the reference device and compared to the Lactate Pro 2. We used the Bland-Altman method to calculate the limits of agreement and used mixed effect models to compare instruments and sample sites. A total of 49 intensive care patients with elevated lactate and 11 healthy volunteers with elevated lactate were included. Results There was no significant difference in measured lactate between Lactate Pro 2 and the reference method using arterial blood in either the healthy volunteers or the intensive care patients. Capillary lactate measurement in the fingertip and earlobe of intensive care patients was 47% (95% CI (29 to 68%), p < 0.001) and 27% (95% CI (11 to 45%), p < 0.001) higher, respectively, than the corresponding arterial blood lactate. In the healthy volunteers, we found that capillary blood lactate in the fingertip was 14% higher than arterial blood lactate (95% CI (4 to 24%), p = 0.003) and no significant difference between capillary blood lactate in the earlobe and arterial blood lactate. Conclusion Our results showed that the handheld Lactate Pro 2 had good agreement with the reference method using arterial blood in both intensive care patients and healthy volunteers. However, we found that the agreement was poorer using venous blood in both groups. Furthermore, the earlobe may be a better sample site than the fingertip in intensive care patients.publishedVersio

Prehospital Whole Blood Transfusion Programs in Norway

Background: Prehospital management of severe hemorrhage has evolved significantly in Norwegian medical emergency services in the last 10 years. Treatment algorithms for severe bleeding were previously focused on restoration of the blood volume by administration of crystalloids and colloids, but now the national trauma system guidelines recommend early balanced transfusion therapy according to remote damage control resuscitation principles. Materials and Methods: This survey describes the implementation, utilization, and experience of the use of low titer group O whole blood (LTOWB) and blood components in air ambulance services in Norway. Medical directors from all air ambulance bases in Norway as well as the blood banks that support LTOWB were invited to participate. Results: Medical directors from all 13 helicopter emergency medical services (HEMS) bases, the 7 search and rescue (SAR) helicopter bases, and the 4 blood banks that support HEMS with LTOWB responded to the survey. All HEMS and SAR helicopter services carry LTOWB or blood components. Four of 20 (20%) HEMS bases have implemented LTOWB. A majority of services (18/20, 90%) have a preference for LTOWB, primarily because LTOWB enables early balanced transfusion and has logistical benefits in time-critical emergencies and during prolonged evacuations. Conclusion: HEMS services and blood banks report favorable experiences in the implementation and utilization of LTOWB. Prehospital balanced blood transfusion using whole blood is feasible in Norway

Implementation of a low-titre whole blood transfusion program in a civilian helicopter emergency medical service

Background: Early balanced transfusion is associated with improved outcome in haemorrhagic shock patients. This study describes the implementation and evaluates the safety of a whole blood transfusion program in a civilian helicopter emergency medical service (HEMS). Methods: This prospective observational study was performed over a 5-year period at HEMS-Bergen, Norway. Patients in haemorrhagic shock receiving out of hospital transfusion of low-titre Group O whole blood (LTOWB) or other blood components were included. Two LTOWB units were produced weekly and rotated to the HEMS for forward storage. The primary endpoints were the number of patients transfused, mechanisms of injury/illness, adverse events and survival rates. Informed consent covered patient pathway from time of emergency interventions to last endpoint and subsequent data handling/storage. Results: The HEMS responded to 5124 patients. Seventy-two (1.4%) patients received transfusions. Twenty patients (28%) were excluded due to lack of consent (16) or not meeting the inclusion criteria (4). Of the 52 (100%) patients, 48 (92%) received LTOWB, nine (17%) received packed red blood cells (PRBC), and nine (17%) received freeze-dried plasma. Of the forty-six (88%) patients admitted alive to hospital, 35 (76%) received additional blood transfusions during the first 24 h. Categories were blunt trauma 30 (58%), penetrating trauma 7 (13%), and nontrauma 15 (29%). The majority (79%) were male, with a median age of 49 (IQR 27–70) years. No transfusion reactions, serious complications or logistical challenges were reported. Overall, 36 (69%) patients survived 24 h, and 28 (54%) survived 30 days. Conclusions: Implementing a whole blood transfusion program in civilian HEMS is feasible and safe and the logistics around out of hospital whole blood transfusions are manageable.publishedVersio

Validation of a point-of-care capillary lactate measuring device (Lactate Pro 2)

Background The measurement of lactate in emergency medical services has the potential for earlier detection of shock and can be performed with a point-of-care handheld device. Validation of a point-of-care handheld device is required for prehospital implementation. Aim The primary aim was to validate the accuracy of Lactate Pro 2 in healthy volunteers and in haemodynamically compromised intensive care patients. The secondary aim was to evaluate which sample site, fingertip or earlobe, is most accurate compared to arterial lactate. Methods Arterial, venous and capillary blood samples from fingertips and earlobes were collected from intensive care patients and healthy volunteers. Arterial and venous blood lactate samples were analysed on a stationary hospital blood gas analyser (ABL800 Flex) as the reference device and compared to the Lactate Pro 2. We used the Bland-Altman method to calculate the limits of agreement and used mixed effect models to compare instruments and sample sites. A total of 49 intensive care patients with elevated lactate and 11 healthy volunteers with elevated lactate were included. Results There was no significant difference in measured lactate between Lactate Pro 2 and the reference method using arterial blood in either the healthy volunteers or the intensive care patients. Capillary lactate measurement in the fingertip and earlobe of intensive care patients was 47% (95% CI (29 to 68%), p < 0.001) and 27% (95% CI (11 to 45%), p < 0.001) higher, respectively, than the corresponding arterial blood lactate. In the healthy volunteers, we found that capillary blood lactate in the fingertip was 14% higher than arterial blood lactate (95% CI (4 to 24%), p = 0.003) and no significant difference between capillary blood lactate in the earlobe and arterial blood lactate. Conclusion Our results showed that the handheld Lactate Pro 2 had good agreement with the reference method using arterial blood in both intensive care patients and healthy volunteers. However, we found that the agreement was poorer using venous blood in both groups. Furthermore, the earlobe may be a better sample site than the fingertip in intensive care patients

Cold-stored whole blood in a Norwegian emergency helicopter service: an observational study on storage conditions and product quality

BACKGROUND Increasing numbers of emergency medical service agencies and hospitals are developing the capability to administer blood products to patients with hemorrhagic shock. Cold‐stored whole blood (WB) is the only single product available to prehospital providers who aim to deliver a balanced resuscitation strategy. However, there are no data on the safety and in vitro characteristics of prehospital stored WB. This study aimed to describe the effects on in vitro quality of storing WB at remote helicopter bases in thermal insulating containers. STUDY DESIGN AND METHODS We conducted a two‐armed single‐center study. Twenty units (test) were stored in airtight thermal insulating containers, and 20 units (controls) were stored according to routine procedures in the Haukeland University Hospital Blood Bank. Storage conditions were continuously monitored during emergency medical services missions and throughout remote and blood bank storage. Hematologic and metabolic variables, viscoelastic properties, and platelet (PLT) aggregation were measured on Days 1, 8, 14, and 21. RESULTS Storage conditions complied with the EU guidelines throughout remote and in‐hospital storage for 21 days. There were no significant differences in PLT aggregation, viscoelastic properties, and hematology variables between the two groups. Minor significantly lower pH, glucose, and base excess and higher lactate were observed after storage in airtight containers. CONCLUSION Forward cold storage of WB is safe and complies with EU standards. No difference is observed in hemostatic properties. Minor differences in metabolic variables may be related to the anaerobic conditions within the thermal box

A whole blood based resuscitation strategy in civilian medical services: Experience from a Norwegian hospital in the period 2017–2020

Background: Civilian and military guidelines recommend early balanced transfusion to patients with life-threatening bleeding. Low titer group O whole blood was introduced as the primary blood product for resuscitation of massive hemorrhage at Haukeland University Hospital, Bergen, Norway, in December 2017. In this report, we describe the whole blood program and present results from the first years of routine use. Study design and methods: Patients who received whole blood from December 2017 to April 2020 were included in our quality registry for massive transfusions. Post-transfusion blood samples were collected to analyze isohemagglutinin (anti-A/-B) and hemolysis markers. Administration of other blood products, transfusion reactions, and patient survival (days 1 and 30) were recorded. User experiences were surveyed for both clinical and laboratory staff. Results: Two hundred and five patients (64% male and 36% female) received 836 units in 226 transfusion episodes. Patients received a mean of 3.7 units (range 1–35) in each transfusion episode. The main indications for transfusion were trauma (26%), gastrointestinal (22%), cardiothoracic/vascular (18%), surgical (18%), obstetric (11%), and medical (5%) bleeding. There was no difference in survival between patients with blood type O when compared with non-group O. Haptoglobin level was lower in the transfusion episodes for non-O group patients, however no clinical hemolysis was reported. No patients had conclusive transfusion-associated adverse events. Both clinical and laboratory staff preferred whole blood to component therapy for massive transfusion. Discussion: The experience from Haukeland University Hospital indicates that whole blood is feasible, safe, and effective for in-hospital treatment of bleeding