Long-distance air medical transport of extremely low birth weight infants with pneumoperitoneum

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1 (2008) 28, r 2008 Nature Publishing Group All rights reserved /08 $30 ORIGINAL ARTICLE Long-distance air medical transport of extremely low birth weight infants with RM McAdams, SA Dotzler, GL Pole and JD Kerecman Department of Neonatology, US Naval Hospital Okinawa and 18th Medical Group, Kadena Air Base, Japan Objective: Long-distance air transport (LDAT) of infants with for pediatric surgical evaluation has not been previously reported. We examined whether extremely low birth weight (ELBW) infants with and without would tolerate transport differently. Study Design: A retrospective cohort study was conducted comparing ELBW infants diagnosed with to other ELBW infants transported >2000 miles by a trained team from a US Department of Defense tertiary care neonatal intensive care unit in Okinawa, Japan. Result: Between 2000 and 2006, 49 air transports met study criteria. Seven of the 49 (14%) infants had at time of transport. The average distance flown was 5346 miles per transport. The 49 infants had a median gestational age of 25 weeks and birth weight of 761±127 g. ELBW infants without were transported at a median 58 days of life (DOL; range 30 to 91 days) compared to infants with, who were transported at a median 8 DOL (range 6 to 14 days). At the time of LDAT, infants with were significantly smaller, receiving more arterial and central venous access, more pressors for hypotension, and more mechanical ventilation compared to ELBW infants transported without. In-flight patient-related medical issues were similar regardless of underlying diagnosis or age at the time of transport. Conclusion: Successful LDAT of ELBW infants, including critically ill infants with intestinal perforation, is possible. Use of personnel, experienced and trained in aviation transport physiology, overcomes the extreme physiologic operating environment associated with LDATs. (2008) 28, ; doi: /jp ; published online 28 February 2008 Keywords: air transport; ELBW; infant; ; SIP Correspondence: Dr RM McAdams, Department of Neonatology, US Naval Hospital Okinawa, PSC 482, Box 2479, FPO, AP , Japan. Received 21 August 2007; revised 16 December 2007; accepted 27 December 2007; published online 28 February 2008 Introduction The neonatal transport environment remains one of the most physiologically stressful situations for extremely low birth weight (ELBW, p1000 g) infants. Air transport of sick ELBW infants may result in exposure to physiologic stressors related to environmental changes at altitude, including decreased humidity, temperature and atmospheric pressure, and partial pressure of oxygen, as well as gas expansion. 1 Infants with are at risk for expansion of intra-abdominal free air which may lead to compromised enteric blood flow, discomfort, impaired respiratory mechanics and further decompensation in already critically ill patients. Additional stressors that occur during long-distance air transport (LDAT) affecting patients and practitioners include increased motion, vibration and noise, as well as working space constraints and fatigue, for example, from crossing multiple time zones. 2 When transporting sick infants, these potential risks of LDAT need to be considered and require an experienced transport team to manage complicated in-flight situations. To examine the safety and survival of LDAT for ELBW infants, we report a case series of critically ill infants with clinical and radiographic evidence of intestinal perforation that required pediatric surgical evaluation compared to a cohort without who underwent international interhospital transfer by trans-pacific air transport. Our objective was to examine whether transported ELBW infants with and without would tolerate transfer differently and to provide guidance to practitioners considering LDAT of neonates. Methods A retrospective cohort analysis was performed using medical records of all ELBW neonates (BW p1000 g) that were transported by the neonatal intensive care unit (NICU) transport team from Kadena Air Base and US Naval Hospital Okinawa (USNHO), Japan to other military NICUs in the United States between January 2000 and December Inclusion criteria were met if the neonate underwent LDAT, defined as air transport >2000 statute miles. The definition for LDAT was decided relative to the distances we typically transport infants. Pneumoperitoneum was diagnosed

2 Air transport of infants with 331 based on evidence of free air on abdominal radiograph. In all cases of infants with, patients were placed on broadspectrum antibiotics and made NPO with bowel decompression using a Replogle tube. For all transported infants, parental consent was obtained prior to LDAT. The Institutional Review Board of the US Naval Hospital Okinawa/Navy Medicine West approved the study. Demographic data collected included: estimated gestational age, birth weight, gender, day of life of air transport, weight at transport, central and arterial lines, need for inotropes during transport, need for mechanical ventilation for air transport, inborn versus outborn (born at an medical facility in the Western Pacific other than USNHO) status, type of military aircraft utilized for LDAT and miles flown on air transport. For infants with, additional data were collected including patent ductus arteriosus (PDA) demonstrated by an echocardiogram, use of a cyclooxygenase inhibitor or corticosteroids, whether feeds were given prior to the diagnosis of, day of life of diagnosis, use of a peritoneal drainage (PD) with Penrose drain placement done by a general surgeon prior to LDAT, duration of transport, final diagnosis for etiology of, treatment performed and outcome. Infants with were considered to have survived LDAT if they were still alive >7 days beyond the day of transport since any death occurring shortly after LDAT may have been attributed to transport-related complications. In-flight patient-complication data was obtained from comments made by the transport team on the medical record and/or transport record. The NICU located at the USNHO, Japan serves as the regional referral center for the Western Pacific (WESTPAC) region, including Korea, Mainland Japan and the Marianas. All aeromedical transports were performed by one of our NICU teams trained in neonatal transport, as well as a standard US Air Force aeromedical evacuation team attached to the medical transport aircraft. By our local policy, critically ill infants required a minimum of a neonatologist and a NICU nurse on the transport. To promote a thorough understanding of altitude physiology, familiarity of all transport equipment and an appreciation of the limitations of aeromedical care transport, all members of the WESTPAC Neonatal Transport Team completed an Aeromedical Transport Course taught by the NICU Neonatal Transport Team leaders. In addition, all members underwent annual training and testing to assess proper use of transport medical equipment. To ensure safety for aeromedical transport, by US Air Force regulation, all models of medical equipment used for transport undergo airworthiness testing at the US Air Force School of Aerospace Medicine facility, Brooks City-Base, TX, prior to initial in-flight patient use. All electrical equipment had been previously tested to ensure absence of electromagnetic emission production that could interfere with the aircraft or be affected by aircraft emissions. Demographic data were described and statistical analysis performed using Stata/IC 10.0 (StataCorp LP, College Station, TX, USA). Continuous variables were compared using Student s t-test or Wilcoxon rank-sum test. Categorical variables were compared via Fisher s exact test. Significance was accepted at P<0.05. Results Between January 2000 and December 2006, 65 ELBW infants were transported by air, all >520 miles. There were 49 air transports of ELBW infants >2000 miles with the average distance flown of 5346 miles per transport. Forty-five LDATs originated from USNHO to Hawaii (23), California (21) and Washington (1) and 4 outborn LDATs of infants originated at medical facilities in South Korea (2) and Saipan (2) who were then transported to Hawaii. Seven of the 49 infants (14%) were diagnosed with and were transferred for pediatric surgical evaluation. All infants survived air transport (>7 days following LDAT). Demographic features of the ELBW LDAT cohort are given in Table 1. There are no significant differences in gestational age or birth weight between infants with and without. However, ELBW infants without were older at time of transport with a median age of 58 days of life (DOL) with a weight at transfer of 1866±1074 g (mean±s.d.) compared to infants with who underwent LDAT at 8 DOL and had a transfer weight of 774±118 g. All infants with were intubated and had central venous line and arterial access during flight while 33% (14/42) of infants without Table 1 Demographics of infants with and without Infants with (n ¼ 7) Infants without P-value (n ¼ 42) GA (weeks) median (IQR) 26 (24 26) 25 (24 26) 0.64 Birth weight (g) 778± ± Male 6/7 23/ Age at transport median (IQR) 8 days (6 14) 58 days (30 91) <0.001 Weight at transport (g) 774± ±1074 <0.001 Arterial access 7/7 7/42 <0.001 Central venous access 7/7 7/42 <0.001 Inotropes in flight 6/7 1/42 <0.001 Intubated for flight 7/7 14/ Outborn 1/7 15/ Miles flown 4912 (±713) 5418 (±888) 0.16 Neonatologist on flight 7/7 23/ Aircraft KC-135 2/6 13/37 C-17 3/6 17/37 C-141 1/6 5/37 C-5 0 2/37 Abbreviations: GA, gestational age; IQR, interquartile range. Data are presented as mean±s.d. for birth weight, weight at transport and miles flown.

3 332 Air transport of infants with Table 2 Demographics of infants with Case no. GA (weeks) BW (g) Gender Apgar (1 min) Apgar (5 min) Mode of ventilatory support a Inotropic agents PDA Cyclo-oxygenase inhibitor Postnatal steroids EBM feeds M 2 6 CMV M 4 8 CMV F 6 8 ncpap M 4 7 ncpap M 1 7 ncpap M 1 1 ncpap M 8 8 CMV Total 26 b 778 c 6/7 M 4 b 7 b 4/7 ncpap 7/7 4/7 4/7 5/7 4/7 Abbreviations: BW, birth weight; CMV, conventional mechanical ventilation; EBM, expressed breast milk; F, female; GA, gestational age; M, male; ncpap, nasal continuous positive airway pressure; PDA, patent ductus arteriosus. a Ventilator mode at time of. b Median. c Mean. Table 3 Air transport and outcome data of infants with Case no. Diagnosis of (DOL) Peritoneal Drain Conventional mechanical ventilation for transport Time of transport (DOL) Miles flown Transport duration (hours) Diagnosis Surgery Outcome SIP Died DOL SIP + Survived NEC + Survived Pyloric + Survived atresia SIP + Survived SIP Survived SIP Survived Total 8 a 5/7 7/7 8 a 4912 b 15 b 5/7 with SIP 4/7 6/7 Abbreviations: DOL, days of life; NEC, necrotizing enterocolitis; SIP, spontaneous intestinal perforation. Transport duration is the sum of ground time and in-flight time. a Median. b Mean. were intubated for flight (P ¼ 0.002) and 14% (6/42) had central venous access (P<0.001) and 17% (7/42) had arterial lines for the flight (P<0.001). The majority of infants in both groups were born at USNHO, Japan. The top three reasons for transport in the nonpneumoperitonium group were (1) retinopathy of prematurity evaluation and treatment, (2) long-term multidisciplinary care requirements related to prematurity and (3) PDA requiring surgical ligation. Table 2 summarizes the demographic information of infants with. The majority of infants with were male (6 of 7), all 7 received vasoactive medications (dopamine, dobutamine and/or epinephrine) for hypotension in the first week of life, 5 of the 7 received postnatal steroids and 4 of the 7 received treatment with a cyclo-oxygenase inhibitor (3 received indomethacin and 1 received mefenamic acid) for PDA. Treatment with both postnatal steroids and a cyclooxygenase inhibitor occurred in 3 of the 5 infants diagnosed with spontaneous intestinal perforation (SIP). No infants were fed formula and 4 of the 7 received trophic feeds with breast milk prior to diagnosis of. One infant (Case no. 1) was outborn and was transferred to our institution by medical air transport on DOL 3. Table 3 summarizes interventions, events related to LDAT and outcomes in the study cohort following diagnosis of. The s were recognized at median age of 8 DOL (median) with transport occurring at the same DOL. Five of the 7 infants had peritoneal drains placed by general surgeons prior to transport. The majority of infants (5 of 7)

4 Air transport of infants with 333 were diagnosed with SIP of which 4 received peritoneal drains prior to LDAT with 2 requiring subsequent laparotomy. One infant (Case no. 3) initially presented with finding consistent with SIP on DOL 6 and had PD performed as a temporizing measure. Following LDAT on DOL 10, she developed a second intestinal perforation on DOL 17 requiring an exploratory laparatomy with segmental small and large bowel resection, jejunostomy, mucous fistula and gastrostomy and was diagnosed with necrotizing enterocolitis (NEC). After LDAT, Case no. 4 had an exploratory laparotomy and was diagnosed with gastric outlet obstruction. This infant subsequently developed epidermolysis bullosa and was thought to have Carmi syndrome. A total of 6 of 7 infants survived to hospital discharge with one infant death (Case no. 1) at DOL 96. Long-term morbidity and mortality data beyond hospital discharge was not available. There were few recorded complications on the 49 ELBW infant transports. In the non cases there were three infants that had significant desaturations ( bronchopulmonary dysplasia spells) resulting in hand bagging, sedation and/or paralytics. Two of these three infants received increased oxygen support using nasal continuous positive airway pressure or nasal cannula during flight. Finally, increased abdominal distension occurred in one infant during flight who was subsequently not fed. In the group the only recorded complication was one patient with increasing abdominal girth. All 49 infants survived the LDAT. NICU transport team personnel on all 49 LDATs included 1 to 2 nurses and 1 to 2 medical technicians. There were 30 transports in which a neonatologist, 1 to 2 nurses, and 1 to 2 medical technicians accompanied the infant, including the 7 infants with who were transported an average of 4912 miles per LDAT, with the longest being 6527 miles. All transports occurred at a cabin altitude of <8000 ft, with a typical range of between 5000 and 8000 ft. Discussion US government employees and their family members serving overseas may require international interhospital transfer to provide optimal care for medical conditions. Due to limited subspecialty care resources available to us, and the long-term care issues facing the neonatal patient, we transport NICU patients with regular frequency to the United States. As described in our cohort study, in ELBWs requires prompt pediatric surgical evaluation, which is not available at our center, necessitating the need for trans-pacific international interhospital transfer typically utilizing US military cargo/transport aircraft. Pneumoperitoneum in the majority of ELBW infants in our study was secondary to SIP, an acquired form of neonatal bowel disease with an estimated incidence of 1:5000 live births. 3 Our infants with SIP fell into the late onset category (acquiring SIP on average between 7 and 10 DOL) 2 related to known postnatal risk factors 3,4 such as exposure to indomethacin and glucocorticoids, presence of a PDA and use of vasoactive pressors within 14 days of perforation. The mortality for ELBW infants with NEC or SIP has been shown to be approximately 50%. 5 There are several controversial aspects of the surgical management of these infants. It is unknown whether simple PD or laparotomy (and likely intestinal resection) should be the initial surgical therapy for ELBW infants and whether the same procedure should be used for both disorders. 6 The long-term effects of LDAT on infants with SIP or NEC managed with PD are not known. Further studies will hopefully clarify the optimal treatment for infants with SIP or NEC. 7 Although laparotomy may be the preferable surgical option for infants with SIP or NEC in regards to long-term outcome, this requires the availability of an experienced surgeon. Transporting a sick ELBW in an aircraft 4000 miles over the Pacific Ocean is not a risk-free endeavor and therefore maximizing patient stability prior to transport is essential to prevent catastrophic in-flight outcomes. In cases where infants with require LDAT for pediatric surgical evaluation, we advocate abdominal decompression, preferably with PD, for a temporizing measure prior to transport. PD involves a bedside procedure where 1 or 2 Penrose drains are placed through a small incision in the lower abdominal quadrants. In these infants, PD drains fluid or decreases air levels, relieves symptoms of abdominal compartment syndrome and may allow infants to better tolerate subsequent laparotomy. 8 At altitude, we speculate that PD decreases intra-abdominal pressure related to expansion of trapped abdominal air, thus facilitating patient stability by allowing for better enteric circulation and preventing respiratory compromise. In our cohort study, two infants underwent LDAT without PD. These infants had bowel decompression using a Replogle tube with intermittent in-flight manual syringe suction and were flown with an altitude restriction of 3000 ft to minimize intra-abdominal gas expansion. We do not advocate air transport without a PD if there are concerns for intra-abdominal gas expansion (for example, secondary to SIP), since gastric suction devices will only decompress bowel gas and will not address intraabdominal free air. Intubation of the gastrointestinal tract, with a Replogle or sump gastric tube, is utilized for decompression of the bowel lumen. However, bowel air removal is limited secondary to the Replogle or sump gastric tube tip being located in the stomach; therefore, decompression is limited by the pyloric sphinchter. 9 Despite many inherent risks with LDAT, all the 49 ELBW infants, including the 7 infants with, were safely transported. These transports require substantial resources, primarily a designated aircraft capable of nonstop LDAT of at least 5000 miles. These particular aircrafts require flight-line personnel and often a high-lift truck to load a pallet of medical equipment supplies including the patients in a transport isolette, medical gases and other equipment into the aircraft. Our in-flight personnel

5 334 Air transport of infants with included the flight crew (pilots and others), an Air Force medical evacuation team (flight nurses and techniciansfoften these missions carry multiple patients of a variety of ages, conditions and degrees of illness) and an air transport-trained neonatal transport team. NICU transport team configuration is determined prior to every flight by the neonatologists at USNHO based on the acuity of the infant requiring transport and the distance/duration of the LDAT; more acutely ill infants and infants undergoing longer missions (for example, >5000 miles, 15 h in-flight duration) being supported by larger teams to account for fatigue and promote patient safety. Time-sensitive neonatal transport of critically ill infants, such as the ELBW infants with perforated bowel reported in this study, can potentially prevent time-dependent complications associated with tissue injury. However, transport of patients, especially labile ELBW infants, should only be attempted when the benefit outweighs the risks. There are many risks associated with LDAT, many of which can be avoided by an experienced transport team familiar with the capabilities of the transport aircraft, in-flight policies and procedures, and the transport equipment. A fundamental aspect of LDAT is careful in-flight monitoring. We utilize i-stat handheld blood gas analyzers (Abbott Point of Care Inc., East Windsor, NJ, USA) to assess in-flight blood gases, including electrolyte and hematocrit levels. Our neonatal transport isolette is equipped with a Propaq Encore (Welch Allyn, Beaverton, OR, USA) vital signs monitor and we use a MiniOx 3000 oxygen monitor (MSA, Pittsburgh, PA, USA) to assess the fractional inspiration of inspired oxygen. Due to the constant high noise levels on the military aircrafts and the need for ear protection, auditory alarms are virtually undetectable, necessitating vigilant observation of the infant s monitors and intravenous pumps to detect visual alarms or malfunctioning equipment. Depending on the type of aircraft, diminished workspace and lighting may affect the ability to comfortably assess a transported infant. The use of a headlamp facilitates improved visual capabilities and a large NICU transport team with in-flight shift rotation promotes attentiveness to the infant and transport equipment. A direct visual line and an accessible path to the infant and the equipment are essential to avoid a delayed response in the event of a threatening or present adverse situation. Despite proper safety precautions, not all of the physiologic effects of aviation can be avoided and these may result in adverse consequences to the patient. The long-term effects on infants of acceleration/deceleration forces secondary to takeoff and landing, cabin pressure changes, excessive sound, vibration, motion and temperature changes associated with air transport are not fully understood. The stressors also affect the neonatal transport team members, which may contribute to fatigue, making it essential that care providers stay well hydrated and rotate shifts to promote focused care in flight. Long-distance international interhospital transfer by air transport of critically ill ELBW infants with intestinal perforation can be achieved. Peritoneal drainage provided successful temporizing stabilization following intestinal perforation in ELBW infants in our study; however, due to the small number of patients studied and lack of randomization to PD, the relative benefits of PD needs further investigation before this practice can be advocated for infants with requiring air transport. In addition to significant resources, these long-distance transfers require an experienced transport team in which each member is aware of the effects of aviation physiology on the patient s preexisting illness. A high level of coordination between the transport team, crewmembers, ground operation crews and the accepting medical facility, before and during the transport based on the patient s condition, is required to accomplish a successful LDAT. Acknowledgments We thank the US Air Force NICU nurses and technicians, the aeromedical evacuation teams, flight-deck crew, aircraft maintenance and ground crew members, and the Theater Patient Movement Requirements Center for their hard work and dedication. They are essential for making our neonatal air transports safe and successful. Disclosure The opinions expressed in this paper are solely those of the authors and do not represent the views of the US Air Force, US Navy, Department of Defense or the US Government. References 1 Section on Transport Medicine, American Academy of Pediatrics. Transport physiology and stresses of transport, In: Woodward GA, Insoft RM, Kleinman ME (eds). Guidelines for Air and Ground Transport of Neonatal and Pediatric Patients, 3rd edn. American Academy of Pediatrics: Elk Grove, 2007, pp Samuels MP. The effects of flight and altitude. Arch Dis Child 2004; 89: Attridge JT, Clark R, Walker MW, Gordon PV. New insights into spontaneous intestinal perforation using a national data set: (1) SIP is associated with early indomethacin exposure. J Perinatol 2006; 26: Gordon PV, Swanson JR, Attridge JT, Clark R. Emerging trends in acquired neonatal intestinal disease: is it time to abandon Bell s criteria? J Perinatol 2007; 27: Blakely ML, Lally KP, McDonald S, Brown RL, Barnhart DC, Ricketts RR. Post operative outcomes of extremely low birth-weight infants with necrotizing enterocolitis or isolated intestinal perforation: a prospective cohort study by the NICHD neonatal research network. Ann Surg 2005; 241: Moss RL, Dimmitt RA, Henry MCW, Geraghty N, Efron B. A meta-analysis of peritonealdrainage versuslaparotomy for perforated necrotizing enterocolitis. J Pediatr Surg 2001; 3: Blakely ML, Tyson JE, Lally KP, McDonald S, Stoll BJ, Stevenson DK, et al., NICHD Neonatal Research Network. Laparotomy versus peritoneal drainage for necrotizing enterocolitis or isolated intestinal perforation in extremely low birth weight infants: outcomes through 18 months adjusted age. Pediatrics 2006; 117: e680 e Grosfeld JL. Peptic ulcer and other conditions of the stomach. In: Grosfeld JL, O Neill JA, Coran AG, Fonkalsrud EW (eds). Pediatric Surgery. Mosby: Philadelphia, 2006, pp Harbinson SP. Intubation of the stomach and small intestines. In: Yeo CJ, Dempsey DT, Klein AS, Pemberton JH, Peters JH (eds). Shackelford s Surgery of the Alimentary Tract. Saunders: Philadelphia, 2006, pp

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