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In-Flight Pharmacological Management of Patients with Acute Mental Health Disturbance
Air Medical Journal 37 (2018) 115–119
Contents lists available at ScienceDirect
Air Medical Journal j o u r n a l h o m e p a g e : h t t p : / / w w w. a i r m e d i c a l j o u r n a l . c o m /
Original Research
In-Flight Pharmacological Management of Patients with Acute Mental Health Disturbance Brian Wilkinson, MBBS, FRCA 1, James Garwood, BMBS, FRCA, MAcadMEd, DipRTM.RCS(Ed), PGCClinEd 1,2, Stephen Langford, FAFPHM, FRACGP, FACAsM, AFRACMA, DipRACOG, DipAvMed, GAICD 1,* 1 2
Royal Flying Doctor Service (Western Operations), Jandakot, WA, Australia Plymouth Hospitals NHS Trust, Anaesthetics Department, Derriford Hospital, Derriford Rd, Crownhill, Plymouth, Devon, United Kingdom
A B S T R A C T
Objective: Patients can be transferred many hundreds of kilometers with acute mental health disturbance for specialist mental health services in Western Australia. Methods: A retrospective notes review of Royal Flying Doctor Service Western Operations records was undertaken over a 4-month period. Patients were identified from the transfer database by mental health diagnosis. Benzodiazepine and antipsychotic doses were converted into a reference drug per class for comparison. Results: One hundred ten patients underwent air transfer in a total of 130 flights. Over 80% of patients were involuntary patients being transferred for specialist psychiatric evaluation and management in an inpatient mental health unit. Over half of the patients required no in-flight sedation, and around 80% of patients were managed with standard doses of first-line agents (haloperidol, midazolam, and diazepam). A small number of patients required alternative agents for refractory sedation, most commonly ketamine and propofol. There were no statistically significant differences for in-flight medication by sex, ethnicity, or substance misuse status. Conclusions: The rate of in-flight incidents including violence remained low. Transfers of patients with acute mental health disturbance are challenging, and quality preflight assessment and in-flight care are required to minimize the associated risks. Copyright © 2018 Air Medical Journal Associates. Published by Elsevier Inc. All rights reserved.
Air medical evacuation of psychiatric patients was initially described from a theater of war1 and is generally considered to have been first undertaken during World War II. Flaherty2 described air evacuation of psychiatric casualties from Guadalcanal and noted that psychotic patients posed a greater danger to air safety than psychoneurotic patients and that the physical and psychological stressors of air medical evacuation could exacerbate the condition of psychotic patients. During World War II, the principles of risk assessment, mechanical restraint, appropriately trained escorts, use of sedation, and sympathetic handling were established. To this day, these principles remain applicable to the transportation of mentally disturbed patients, both civilian and military.1
* Address for correspondence: Stephen Langford, FAFPHM, FRACGP, FACAsM, AFRACMA, DipRACOG, DipAvMed, GAICD, Royal Flying Doctor Service (Western Operations), 3-5 Eagle Drive, Jandakot, Perth, WA, Australia 6163 E-mail address: [email protected] (S. Langford).
Paraldehyde or barbiturates were used as sedatives during World War II psychiatric evacuations1; however, the deep sedation associated with these agents has led to these agents being superseded by newer agents, predominantly atypical antipsychotics and benzodiazepines. The risks of toxicity, especially arrhythmias with antipsychotics and respiratory depression with benzodiazepines, ensure these drugs must be used judiciously to bring benefit and not harm. The Royal Flying Doctor Service Western Operations (RFDSWO) has been undertaking air medical transportation of patients with acute mental health disturbance in Western Australia since 1982.3 Langford4 reviewed 122 Royal Flying Doctor Service (RFDS) patient transfers over a 6-month period. Ninety-four percent of patients transferred were involuntary patients referred under the Mental Health Act.5 Most patients (70%) were recorded as having received preflight sedation, and 86% were transferred by an RFDS nurse and police escort. Just over half of the patients in Langford’s study received in-flight sedation, most commonly intravenous midazolam.
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B. Wilkinson et al. / Air Medical Journal 37 (2018) 115–119
Table 1 Demographics of Patients With Acute Mental Disturbance Transferred by the Royal Flying Doctor Service Western Operations Demographic
n
%
Mean Age (y)
SD Age (y)
Mean Weight (kg)
SD Weight (kg)
Recorded Illicit Drug Use (n)
Recorded Illicit Drug Use (%)
All Male Female Aboriginal/Torres Strait Islander (ATSI) Non-ATSI ATSI male ATSI female Non-ATSI male Non-ATSI female
110 72 38 51
100 65.5 34.5 46.4
36.0 36.1 35.5 31.6
15.2 14.7 16.4 11.8
77.2 80.6 70.4 75.8
18.0 19.3 12.8 19.2
39 27 12 23
34.5 37.5 31.6 45.1
59 33 18 39 20
53.6 30 16.4 35.5 18.2
36.5 31.9 31.1 36.2 36.7
15 11.9 12.1 14.7 14.9
78.3 80.4 71.1 82.6 69.9
17.0 20.6 11.0 16.8 14.4
16 16 7 11 5
27.1 48.5 38.9 28.2 25
SD = standard deviation.
Table 2 Legalities of Transfers Mental Health Forms
n
%
Demographic
N
%
Form 1 (referral order) Form 3 (transport order) Previously on community treatment order Form 11 (revocation of community treatment order) Form 5 (detention for further assessment) Form 6 (involuntary patient order)
90 91 3 2 1 1
81.8 82.7 2.7 1.8 .9 .9
Police escort Mechanical restraint use recorded Forms 1 & 3 completed by RFDS doctor Patients restrained without transport order (Form 3) Voluntary patients/“medical” diagnosis (eg, delirium) In-flight violence
87 84 1 0 15 2
79.1 76.4 .9 0 13.6 1.8
RFDS = Royal Flying Doctor Service.
In-flight violence over the period of 1986 to 2004 was low, with a quoted incidence of 1 in 350 transfers. This study formed part of a larger follow-up project to review the management of patients with acute mental health disturbance who undergo air medical transportation with RFDSWO.
Table 3 In-flight Sedation Given by Medication
Methods A retrospective review of patients transferred by RFDSWO was undertaken with the aim of obtaining a comparative cohort size to the 2004 audit. Patients were identified from the RFDS transfer database by mental health International Classification of Diseases, Ninth Revision diagnosis.6 Patients with mental health as the incident comorbidity rather than the primary diagnosis were excluded. In order to obtain a comparative cohort size with the 2004 audit, a retrospective case notes review was completed for a 4-month period. The clinical transfer record and all other records held by RFDSWO were reviewed. All medications and therapy given while in the care of RFDSWO were considered as in-flight. Data were collated into a 1 line per patient transfer spreadsheet document. Statistical software was used to calculate P values from MannWhitney U7 and Fisher exact tests.8 In order to compare doses of benzodiazepines and antipsychotics given in flight, doses are converted into a reference drug per class. Results In this study, 111 patients were referred to RFDSWO for transfer. One patient was excluded because of being transferred by road ambulance to a nearby mental health unit when adverse weather rendered air medical transfer unsafe. One hundred ten patients underwent RFDS air transfer in a total of 130 flights, with cumulative RFDS care time exceeding 12 days. The RFDS transfer clinical record was available for all patients. The age of patients ranged from 11 to 86 years (mean = 34 years). Table 1 details a demographic breakdown of the patients. Schizophrenia, bipolar affective disorder, and other psychoses accounted for nearly three quarters of the diagnoses. One hundred eight patients were transferred from mainland Western Australia,
Medication
N
%
Median (mg)
Range (mg)
No sedation Midazolama Midazolam, exclude intubated patients Haloperidol Morphinea Morphine, exclude intubated patients Olanzapine Diazepam Promethazine Ketamine Propofol
59 46 43
53.6 41.8 40.2
— 6 5.5
— 1-60 1-20.5
12 4 1
10.9 3.6 .9
8.5 36 3
2-10.5 3-60 —
1 6 4 7 4
.9 5.5 3.6 6.4 3.6
a
10 10 25 125 55
— 5-20 10-50 30-750 50-110
Data skewed by ventilated patients being sedated with morphine and midazolam.
1 patient from the Rottnest Island Nursing Post, and 1 patient from Christmas Island Hospital. Transfer legalities are summarized in Table 2. Medications are prescribed by RFDSWO doctors on the flight assessment when no doctor will be present on board. Additionally, planes are equipped with satellite phones so flight nurses can consult with ground-based RFDSWO doctors. Tables 3 and 4 summarize in-flight medications given during this study. Benzodiazepine equivalent doses are provided as diazepam milligrams using the dose equivelant scale described by Latt and Conigrove.9 Table 5 summarizes nonpharmacologic management in flight. Table 6 summarizes conscious level assessments before and after transfer. The notes review detailed a number of clinical incidents, which are summarized in Table 7. All ventilated transfers of psychiatric patients in Western Australia are reportable to the chief psychiatrist. Discussion All patients transferred by RFDS in Western Australia are accompanied by a flight nurse. A police escort accompanies patients
B. Wilkinson et al. / Air Medical Journal 37 (2018) 115–119
117
Table 4 In-flight Sedation by Reference Drug and Demographic Demographic
n
Total BDZ (mg Diazepam)
Mean BDZ (mg Diazepam)
Standard Deviation BDZ
P Value
Total APs (mg Chlorpromazine)
Mean APs (mg Chlorpromazine)
Standard Deviation APs
P Value
All Male Female ATSI Non-ATSI Illicit drug use No illicit drug use Doctor on flight Nurse only Doctor on flight, intubated excluded
110 72 38 51 59 39 71 50 60 47
216.2 165.2 51 117.5 98.7 76.2 140 136.2 80 92.2
2 2.3 1.3 2.3 1.7 2 2 2.7 1.3 2
4 4.3 3.1 4.2 3.8 3.2 4.3 4.4 3.4 3.1
— .47 — .32 — .33 — .02 — .06
4375 3350 1025 2925 1450 2025 2350 2275 2100 NA
39.8 46.5 27 57.4 24.6 51.9 33.1 45.5 35 NA
127 132.7 116 154.5 96.1 155.6 108.8 139.5 116.6 NA
— .49 — .61 — 1 — .83 — —
APs = antipsychotics; ATSI = Aboriginal/Torres Strait Islander; BDZ = benzodiazepine; NA = not applicable. Benzodiazepine equivalent doses are provided as diazepam milligrams (mg) using the dose equivalence scale described by Latt and Conigrove.9
Table 5 In-flight Monitoring and Management Urinary Catheter
n
%
Observation
N
%
Yes No, penile sheath No RFDS care > 2 hours Urinary catheter if RFDS care > 2 hours RFDS care > 3 hours Urinary catheter if RFDS care > 3 hours
38 1 71 71 30 39 21
34.5 .9 64.5 64.5 42.3 35.5 53.8
Pulse oximetry End-tidal carbon dioxide (ETCO2) ETCO2 if ventilated (n = 3) Conscious level Noninvasive or invasive blood pressure Start + finish basic Obs recorded (SpO2, NIBP, conscious level) Fasted Not fasted Not recorded/unknown
110 4 2 110 108 94 31 58 21
100 3.6 66.7 100 98.2 85.5 28.2 52.7 19.9
NIBP = noninvasive blood pressure; RFDS = Royal Flying Doctor Service; SpO2 = oxygen saturation (%).
Table 6 Conscious Level Assessments Conscious Level on RFDS Arrival
n
%
Conscious Level at Completion of RFDS Transfer
n
%
GCS 15/“alert” GCS 12-15/“verbal”/“drowsy”/“rousable” GCS 8-11/“agitated”/“snoring”/“sedated”/“pain”/“asleep” GCS < 8/intubated/“deeply sedated”/“paralyzed + sedated” Not recorded
55 37 14 4 0
50 33.6 12.7 3.6 0
GCS 15/“alert” GCS 12-15/“verbal”/“drowsy”/“rousable”/“dozing”/“RASS-1” etc GCS 8-11/“Agitated”/“Snoring”/“Sedated”/“Pain”/“Asleep” GCS < 8/intubated/“deeply sedated”/“paralyzed + sedated” Not recorded
42 41 13 4 10
38.2 37.3 11.8 3.6 9.1
GCS = Glagow Coma Scale; RASS = Richmond Agitation-Sedation Scale; RFDS = Royal Flying Doctor Service.
when a Mental Health Act Form 3 (transport order) is in place.5 An RFDS flight is doctor accompanied when the assessing RFDS doctor deems this to be appropriate. A flight is usually doctor accompanied when the patient is unpredictable, has required significant sedation, or is perceived to pose a risk of in-flight violence. Patients are periodically reassessed in order to guide flight staffing and management. The rate of doctor-accompanied flights has increased significantly from 14% in 2004 to 46% in this study (P < .0001). This is further evidence to support Stokes’10 impression that mental health patients have become more challenging to manage in recent years. The management of an agitated or excessively sedated patient in flight is challenging, and this review revealed at least 1 patient when having an RFDS doctor on board would have been advantageous. Two near misses in which a doctor was on board for a second patient but was required for intervention were also noted. The 2 incidents of violence involved the same patient, a 13year-old Aboriginal/Torres Strait Islander male for involuntary mental health admission. The patient was initially assessed as suitable for nurse-only transfer with police escort but remained violent and agitated despite additional sedation. He was deemed to have become unsafe for air travel during airplane taxi and was returned to the
referring hospital. The patient was subsequently transferred the next day with a doctor, nurse, and police escort; however, he was still spitting at staff and needed additional sedation in flight. The majority of patients transferred by RFDSWO either required no in-flight sedation (53.6%) or no greater than midazolam 10 mg and/or haloperidol 10 mg without other agents (78%). Having a doctor on board was associated with a trend of receiving more in-flight benzodiazepines; however, once intubated transfers were excluded, this fell short of statistical significance (P = .06). This may be explained by better identification of patients likely to require inflight sedation; however, care should be taken to ensure that having a doctor on board does not lead to an expectation of deeper sedation. No statistically significant differences were found for inflight sedation given by sex, ethnicity, or history of substance misuse. This contrasts with indigenous patients receiving statistically greater doses of benzodiazepines and antipsychotics at referring centers. In flight, a variety of medications were used in patients who had agitation refractory to RFDS standard agents (midazolam, haloperidol, and diazepam). These included promethazine, propofol, and ketamine. Propofol (50-110 mg) was used in 4 patients; however, 1 patient became obtunded and required the use of an oropharyngeal airway. Le Cong et al11 studied the use of ketamine by bolus
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Table 7 Incidents Identified on Case Notes Review Incident
Demographic
Transfer Details
Preflight Sedation
In-flight Sedation
DR/NO
Details of Incident
Sedation
40 M non-ATSI
Derby-Broome 166 km
Midazolam 5 mg, diazepam 5 mg, clozapine 20 mg
Midazolam 1 mg, propofol 50 mg
DR
Prescription
55 F non-ATSI
Geraldton-Perth 370 km
Quetiapine 600 mg, diazepam (NR)
Midazolam 2 mg, haloperidol 10 mg
NO
Sedation (drug toxicity)
34 M ATSI
Nickol Bay–Broome 647 km
Midazolam 44 mg, haloperidol 5 mg, chlorpromazine 600 mg, diazepam 5 mg
Midazolam 19 mg, haloperidol 10 mg, promethazine 50 mg, propofol 50 mg
DR
Intubated transfer
34 M ATSI
Broome-Perth 1,683 km
As above
DR
Sedation
25 M non-ATSI
Nickol Bay–Perth 1,250 km
Staffing/sedation (drug toxicity)
35 M ATSI
Geraldton-Perth 370 km
Midazolam 36 mg, haloperidol 10 mg, olanzapine 10 mg, clonazepam 6 mg, propofol 100 mg Midazolam 100.5 mg, haloperidol 30 mg, olanzapine 10 mg, clonazepam 2 mg
Morphine 60 mg and midazolam 60-mg infusion Midazolam 6 mg, haloperidol 2.5 mg
Reduced GCS postsedation on aircraft, needed OP airway, was noted to be partially obstructing airway with sedation at referring location Inadequate anticipatory sedation prescribed, additional sedation prescribed after discussion with ground-based RFDS doctor Very agitated at referring location, commenced on chlorpromazine infusion. Still agitated in flight, required sedation ++, became tachypnoea, and saturations decreased. Antibiotics given for possible aspiration/pneumonia. Taken to Broome (planned mental health admission) where intubated in view of likely iatrogenic chlorpromazine overdose after discussion with toxicology. Ventilated transfer of above patient
Staffing
20 F ATSI
Port Hedland–Perth 1,323 km
Sedation
61 M non-ATSI
Prescription
DR
Noted difficult to sedate at referring hospital. Destination changed to emergency department in view of sedation.
None
NO
Midazolam 2 mg, olanzapine 10 mg, diazepam (NR)
Midazolam 5.5 mg, Haloperidol 10.5 mg, ketamine 200 mg
DR
Nickol Bay–Port Hedland 190 km
Diazepam 20 mg
Midazolam 10 mg, haloperidol 2.5 mg
DR
16 M non-ATSI
Geraldton-Bentley 380 km
Lorazepam 1 mg
Midazolam 15 mg
NO
Sedation (drug toxicity)
32 M non-ATSI
Port Hedland–Perth 1,323 km
Midazolam 15 mg, diazepam 20 mg, ketamine 750 mg (100 mg/h infusion)
DR
Staffing/sedation
52 M ATSI
Geraldton-Perth 370 km
Midazolam 17.5 mg, haloperidol 10 mg, olanzapine 30 mg, diazepam 10 mg, ketamine 490 mg (100 mg/hour infusion) Midazolam 127.5 mg, olanzapine 10 mg, diazepam 60 mg, clonazepam 10.5 mg, droperidol 12 mg
None
DR
Intubated transfer
30 F ATSI
Broome-Perth 1,683 km
Morphine 42 mg, midazolam 42-mg infusion
DR
High preflight sedation required. Flight nurse noted slightly prolonged QTc (.458 seconds) and exceeded daily haloperidol (discussed with Graylands). Patient known to have had previous episode of mental illness with ventilated transfer. Flight was uneventful but doctor-accompanied may have been more appropriate. No doctor assessed as required on flight (doctor was on for second patient). Patient agitated in flight; ketamine given for sedation. Sedation exceeded initial prescription for NO flight. Delirium in the context of alcohol withdrawal syndrome. Dropped GCS with sedation in flight; needed jaw thrust, nasopharyngeal airway, and flumazenil. Waited 5 days at referring center for bed to become available. Acute dystonia with IM zuclopenthixol. Was felt to be settled before transfer but became agitated and additional prescription from ground-based RFDS doctor was required. Reportedly difficult to sedate at referring hospital. Ketamine doses discussed with toxicology, felt potential for ketamine toxicity as exceeded maximum daily dose. Destination changed to QEII MC Emergency Department. GCS 5 when picked up by RFDS. Doctor on flight for second patient (this patient assessed as suitable for nurse only). Multiple high doses of different benzodiazepines. GCS 6 at end of transfer; taken to emergency department. Intubated at referring unit as agitated despite sedation. Problematic bronchospasm and oliguria during flight.
Midazolam 35 mg, clonazepam 1 mg, droperidol 10 mg
ATSI = Aboriginal/Torres Strait Islander; DR = doctor; F = female; GCS = Glasgow Coma Scale; IM = intramuscular; M = male; NO = nurse only; NR = not reported; RFDS = Royal Flying Doctor Service. Intubated transfer of patient with tonic-clonic seizure and desvenlafaxine overdose not felt to be a clinical incident as management appropriate (included in study because of coding as suicide attempt).
and, if required, a titrated infusion in 18 patients with acute agitation who did not respond adequately to first-line benzodiazepines and/or antipsychotics. Effective sedation for air medical evacuation was demonstrated without major adverse events. Ketamine was
used in 7 (6.3%) patients in this study under the direct supervision of an RFDSWO doctor. Six patients received bolus ketamine with a total dose range of 30 to 200 mg (mean = 114 mg) without adverse incidents. One patient had a ketamine infusion commenced
B. Wilkinson et al. / Air Medical Journal 37 (2018) 115–119
(100 mg/h [1 mg·kg·h−1]) at the referring hospital, receiving a total dose of 490 mg preflight. The patient remained agitated, and the infusion was continued in flight at the same rate, with additional ketamine given by bolus. The patient received 1240 mg ketamine in total. Refractory agitation was discussed with the state toxicology service, who felt that the patient demonstrated toxicity. Ketamine may have potential as a second-line agent for RFDS in Western Australia; however, the long journey times could lead to dose accumulation so additional study is warranted. The centrally acting alpha-agonists dexmedetomidine and clonidine have gained popularity for sedation in critically ill patients12 because of a reduction in delirium versus benzodiazepines13 and may also warrant further evaluation in the setting of air medical mental health transportation. The optimal depth of sedation for air medical transfer is an alert, calm, and cooperative patient; however, this can be difficult to achieve in patients with significant psychotic symptoms. The sedation should neither be so deep that it places the patient at risk of airway compromise nor so light that the patient is distressed by the experience or distresses other patients on board. One issue RFDS faces is the lack of on-board toilet facilities for restrained patients, and urinary catheters can be invaluable in ensuring patient comfort and prevention of urinary retention. There exists a cohort of patients (< 10%) who demonstrate tolerance and/or resistance to large doses of sedative medication. In-flight incidents demonstrate the challenges of preflight assessment and optimizing sedation. Unfortunately, it was impossible to determine with certainty the conscious level of patients at the start and the end of the period of RFDS care. Wide interindividual variation in reporting consciousness and agitation was present. The majority of patients had a safe conscious level; however, around 1 in 10 patients had a conscious level that risked airway compromise. Level of consciousness at the end of the transfer was similar to pretransfer consciousness. RFDSWO plans to implement the Richmond Agitation-Sedation Scale14 originally developed to qualify sedation depth in the intensive care unit as a means to standardize the reporting of consciousness and sedation in patients with acute psychiatric illness. Half of the transferred patients were accepted into a unit that did not have an emergency department and three quarters to a unit without an on-site intensive care unit. These units have limited capacity to manage patients who have received significant sedation. Future planning of inpatient mental health units should consider the provision of a monitoring facility for sedated patients. The current model for patients who have required significant sedation is assessment in an emergency department after flight; however, this has significant resource and patient flow implications. This study is limited by its retrospective design, and nonrecorded actions cannot be included. There also appears to be greater heterogeneity in this sample, with a lower rate of involuntary patients than Langford’s study.4 Nonetheless, the low rate of excluded
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patients is suggestive that this study represents the cohort of patients with acute mental ill health transferred by RFDS in Western Australia. Conclusions Despite the challenges of transporting acutely agitated patients over large distances, the rate of in-flight violence remained low. The majority of patients transferred in this study did not require large doses of in-flight sedation. A small number of patients required agents for refractory agitation, and deleterious effects of sedative medication were observed. The value of appropriate assessment, preflight sedation, mechanical restraint, and police escort supporting quality in-flight nursing and medical care should not be underestimated. Acknowledgment Mrs. Helen Bartholomew, Database Administrator, RFDS (Western Operations), Jandakot, for their help and work with database searches and records retrieval. References 1. Jones D. Aeromedical transportation of psychiatric patients: historical review and present management. Aviat Space Environ Med. 1980;51:709–716. 2. Flaherty T. Evacuation of wounded air from the battle of Guadalcanal. All Hands Naval Bulletin. 1942;306:2–6. 3. Western Australia Department of Health. Transport of Patients with Disturbed Behaviour from Country Hospitals to Perth. Department of Health and Allied Services Circular. 1983. Available at: http://www.health.wa.gov.au/ circularsnew/pdfs/5712.pdf. Accessed October 3, 2017. 4. Air transport of psychiatric patients in Western Australia. Available at: https:// www.health.wa.gov.au/publications/review/chapters/mental_health_3.7.pdf. Accessed October 3, 2017. 5. Government of Western Australia. Mental Health Act 2014 (MHA 2014). Office of the Chief Psychiatrist. Available at: http://www.chiefpsychiatrist.wa.gov.au. Accessed October 3, 2017. 6. Centers for Disease Control and Prevention. International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). Available at: http:// www.cdc.gov/nchs/about/otheract/icd9/abticd9.Htm. Accessed December 16, 2004. 7. McKnight PE, Najab J. Mann-Whitney U test. In: Corsini Encyclopedia of Psychology. 2010. 8. Upton GJ. Fisher’s exact test. J R Stat Soc Ser A. 1992;155:395–402. 9. Latt N, Conigrove K, Saunders JB, Marshall EJ, Nutt D. Addiction Medicine (Oxford Specialist Handbooks). Oxford, UK: Oxford University Press; 2009. 10. Stokes BA. Review of the admission or referral to and the discharge and transfer practices of public mental health facilities/services in Western Australia. Available at: https://www.mhc.wa.gov.au/media/1288/mental-health-review-report -by-professor-bryant-stokes-am-1.pdf. Accessed October 3, 2017. 11. Le Cong M, Gynther B, Hunter E, Schuller P. Ketamine sedation for patients with acute agitation and psychiatric illness requiring aeromedical retrieval. Emerg Med J. 2012;29:335–337. 12. Pichot C, Ghignone M, Quintin L. Dexmedetomidine and clonidine: from second-to first-line sedative agents in the critical care setting? J Intensive Care Med. 2012;27:219–237. 13. Riker RR, Shehabi Y, Bokesch PM, et al. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA. 2009;301:489–499. 14. Ely EW, Truman B, Shintani A, et al. Monitoring sedation status over time in ICU patients: reliability and validity of the Richmond Agitation-Sedation Scale (RASS). JAMA. 2003;289:2983–2991.
Contents lists available at ScienceDirect
Air Medical Journal j o u r n a l h o m e p a g e : h t t p : / / w w w. a i r m e d i c a l j o u r n a l . c o m /
Original Research
In-Flight Pharmacological Management of Patients with Acute Mental Health Disturbance Brian Wilkinson, MBBS, FRCA 1, James Garwood, BMBS, FRCA, MAcadMEd, DipRTM.RCS(Ed), PGCClinEd 1,2, Stephen Langford, FAFPHM, FRACGP, FACAsM, AFRACMA, DipRACOG, DipAvMed, GAICD 1,* 1 2
Royal Flying Doctor Service (Western Operations), Jandakot, WA, Australia Plymouth Hospitals NHS Trust, Anaesthetics Department, Derriford Hospital, Derriford Rd, Crownhill, Plymouth, Devon, United Kingdom
A B S T R A C T
Objective: Patients can be transferred many hundreds of kilometers with acute mental health disturbance for specialist mental health services in Western Australia. Methods: A retrospective notes review of Royal Flying Doctor Service Western Operations records was undertaken over a 4-month period. Patients were identified from the transfer database by mental health diagnosis. Benzodiazepine and antipsychotic doses were converted into a reference drug per class for comparison. Results: One hundred ten patients underwent air transfer in a total of 130 flights. Over 80% of patients were involuntary patients being transferred for specialist psychiatric evaluation and management in an inpatient mental health unit. Over half of the patients required no in-flight sedation, and around 80% of patients were managed with standard doses of first-line agents (haloperidol, midazolam, and diazepam). A small number of patients required alternative agents for refractory sedation, most commonly ketamine and propofol. There were no statistically significant differences for in-flight medication by sex, ethnicity, or substance misuse status. Conclusions: The rate of in-flight incidents including violence remained low. Transfers of patients with acute mental health disturbance are challenging, and quality preflight assessment and in-flight care are required to minimize the associated risks. Copyright © 2018 Air Medical Journal Associates. Published by Elsevier Inc. All rights reserved.
Air medical evacuation of psychiatric patients was initially described from a theater of war1 and is generally considered to have been first undertaken during World War II. Flaherty2 described air evacuation of psychiatric casualties from Guadalcanal and noted that psychotic patients posed a greater danger to air safety than psychoneurotic patients and that the physical and psychological stressors of air medical evacuation could exacerbate the condition of psychotic patients. During World War II, the principles of risk assessment, mechanical restraint, appropriately trained escorts, use of sedation, and sympathetic handling were established. To this day, these principles remain applicable to the transportation of mentally disturbed patients, both civilian and military.1
* Address for correspondence: Stephen Langford, FAFPHM, FRACGP, FACAsM, AFRACMA, DipRACOG, DipAvMed, GAICD, Royal Flying Doctor Service (Western Operations), 3-5 Eagle Drive, Jandakot, Perth, WA, Australia 6163 E-mail address: [email protected] (S. Langford).
Paraldehyde or barbiturates were used as sedatives during World War II psychiatric evacuations1; however, the deep sedation associated with these agents has led to these agents being superseded by newer agents, predominantly atypical antipsychotics and benzodiazepines. The risks of toxicity, especially arrhythmias with antipsychotics and respiratory depression with benzodiazepines, ensure these drugs must be used judiciously to bring benefit and not harm. The Royal Flying Doctor Service Western Operations (RFDSWO) has been undertaking air medical transportation of patients with acute mental health disturbance in Western Australia since 1982.3 Langford4 reviewed 122 Royal Flying Doctor Service (RFDS) patient transfers over a 6-month period. Ninety-four percent of patients transferred were involuntary patients referred under the Mental Health Act.5 Most patients (70%) were recorded as having received preflight sedation, and 86% were transferred by an RFDS nurse and police escort. Just over half of the patients in Langford’s study received in-flight sedation, most commonly intravenous midazolam.
1067-991X/$36.00 Copyright © 2018 Air Medical Journal Associates. Published by Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.amj.2017.12.002
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Table 1 Demographics of Patients With Acute Mental Disturbance Transferred by the Royal Flying Doctor Service Western Operations Demographic
n
%
Mean Age (y)
SD Age (y)
Mean Weight (kg)
SD Weight (kg)
Recorded Illicit Drug Use (n)
Recorded Illicit Drug Use (%)
All Male Female Aboriginal/Torres Strait Islander (ATSI) Non-ATSI ATSI male ATSI female Non-ATSI male Non-ATSI female
110 72 38 51
100 65.5 34.5 46.4
36.0 36.1 35.5 31.6
15.2 14.7 16.4 11.8
77.2 80.6 70.4 75.8
18.0 19.3 12.8 19.2
39 27 12 23
34.5 37.5 31.6 45.1
59 33 18 39 20
53.6 30 16.4 35.5 18.2
36.5 31.9 31.1 36.2 36.7
15 11.9 12.1 14.7 14.9
78.3 80.4 71.1 82.6 69.9
17.0 20.6 11.0 16.8 14.4
16 16 7 11 5
27.1 48.5 38.9 28.2 25
SD = standard deviation.
Table 2 Legalities of Transfers Mental Health Forms
n
%
Demographic
N
%
Form 1 (referral order) Form 3 (transport order) Previously on community treatment order Form 11 (revocation of community treatment order) Form 5 (detention for further assessment) Form 6 (involuntary patient order)
90 91 3 2 1 1
81.8 82.7 2.7 1.8 .9 .9
Police escort Mechanical restraint use recorded Forms 1 & 3 completed by RFDS doctor Patients restrained without transport order (Form 3) Voluntary patients/“medical” diagnosis (eg, delirium) In-flight violence
87 84 1 0 15 2
79.1 76.4 .9 0 13.6 1.8
RFDS = Royal Flying Doctor Service.
In-flight violence over the period of 1986 to 2004 was low, with a quoted incidence of 1 in 350 transfers. This study formed part of a larger follow-up project to review the management of patients with acute mental health disturbance who undergo air medical transportation with RFDSWO.
Table 3 In-flight Sedation Given by Medication
Methods A retrospective review of patients transferred by RFDSWO was undertaken with the aim of obtaining a comparative cohort size to the 2004 audit. Patients were identified from the RFDS transfer database by mental health International Classification of Diseases, Ninth Revision diagnosis.6 Patients with mental health as the incident comorbidity rather than the primary diagnosis were excluded. In order to obtain a comparative cohort size with the 2004 audit, a retrospective case notes review was completed for a 4-month period. The clinical transfer record and all other records held by RFDSWO were reviewed. All medications and therapy given while in the care of RFDSWO were considered as in-flight. Data were collated into a 1 line per patient transfer spreadsheet document. Statistical software was used to calculate P values from MannWhitney U7 and Fisher exact tests.8 In order to compare doses of benzodiazepines and antipsychotics given in flight, doses are converted into a reference drug per class. Results In this study, 111 patients were referred to RFDSWO for transfer. One patient was excluded because of being transferred by road ambulance to a nearby mental health unit when adverse weather rendered air medical transfer unsafe. One hundred ten patients underwent RFDS air transfer in a total of 130 flights, with cumulative RFDS care time exceeding 12 days. The RFDS transfer clinical record was available for all patients. The age of patients ranged from 11 to 86 years (mean = 34 years). Table 1 details a demographic breakdown of the patients. Schizophrenia, bipolar affective disorder, and other psychoses accounted for nearly three quarters of the diagnoses. One hundred eight patients were transferred from mainland Western Australia,
Medication
N
%
Median (mg)
Range (mg)
No sedation Midazolama Midazolam, exclude intubated patients Haloperidol Morphinea Morphine, exclude intubated patients Olanzapine Diazepam Promethazine Ketamine Propofol
59 46 43
53.6 41.8 40.2
— 6 5.5
— 1-60 1-20.5
12 4 1
10.9 3.6 .9
8.5 36 3
2-10.5 3-60 —
1 6 4 7 4
.9 5.5 3.6 6.4 3.6
a
10 10 25 125 55
— 5-20 10-50 30-750 50-110
Data skewed by ventilated patients being sedated with morphine and midazolam.
1 patient from the Rottnest Island Nursing Post, and 1 patient from Christmas Island Hospital. Transfer legalities are summarized in Table 2. Medications are prescribed by RFDSWO doctors on the flight assessment when no doctor will be present on board. Additionally, planes are equipped with satellite phones so flight nurses can consult with ground-based RFDSWO doctors. Tables 3 and 4 summarize in-flight medications given during this study. Benzodiazepine equivalent doses are provided as diazepam milligrams using the dose equivelant scale described by Latt and Conigrove.9 Table 5 summarizes nonpharmacologic management in flight. Table 6 summarizes conscious level assessments before and after transfer. The notes review detailed a number of clinical incidents, which are summarized in Table 7. All ventilated transfers of psychiatric patients in Western Australia are reportable to the chief psychiatrist. Discussion All patients transferred by RFDS in Western Australia are accompanied by a flight nurse. A police escort accompanies patients
B. Wilkinson et al. / Air Medical Journal 37 (2018) 115–119
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Table 4 In-flight Sedation by Reference Drug and Demographic Demographic
n
Total BDZ (mg Diazepam)
Mean BDZ (mg Diazepam)
Standard Deviation BDZ
P Value
Total APs (mg Chlorpromazine)
Mean APs (mg Chlorpromazine)
Standard Deviation APs
P Value
All Male Female ATSI Non-ATSI Illicit drug use No illicit drug use Doctor on flight Nurse only Doctor on flight, intubated excluded
110 72 38 51 59 39 71 50 60 47
216.2 165.2 51 117.5 98.7 76.2 140 136.2 80 92.2
2 2.3 1.3 2.3 1.7 2 2 2.7 1.3 2
4 4.3 3.1 4.2 3.8 3.2 4.3 4.4 3.4 3.1
— .47 — .32 — .33 — .02 — .06
4375 3350 1025 2925 1450 2025 2350 2275 2100 NA
39.8 46.5 27 57.4 24.6 51.9 33.1 45.5 35 NA
127 132.7 116 154.5 96.1 155.6 108.8 139.5 116.6 NA
— .49 — .61 — 1 — .83 — —
APs = antipsychotics; ATSI = Aboriginal/Torres Strait Islander; BDZ = benzodiazepine; NA = not applicable. Benzodiazepine equivalent doses are provided as diazepam milligrams (mg) using the dose equivalence scale described by Latt and Conigrove.9
Table 5 In-flight Monitoring and Management Urinary Catheter
n
%
Observation
N
%
Yes No, penile sheath No RFDS care > 2 hours Urinary catheter if RFDS care > 2 hours RFDS care > 3 hours Urinary catheter if RFDS care > 3 hours
38 1 71 71 30 39 21
34.5 .9 64.5 64.5 42.3 35.5 53.8
Pulse oximetry End-tidal carbon dioxide (ETCO2) ETCO2 if ventilated (n = 3) Conscious level Noninvasive or invasive blood pressure Start + finish basic Obs recorded (SpO2, NIBP, conscious level) Fasted Not fasted Not recorded/unknown
110 4 2 110 108 94 31 58 21
100 3.6 66.7 100 98.2 85.5 28.2 52.7 19.9
NIBP = noninvasive blood pressure; RFDS = Royal Flying Doctor Service; SpO2 = oxygen saturation (%).
Table 6 Conscious Level Assessments Conscious Level on RFDS Arrival
n
%
Conscious Level at Completion of RFDS Transfer
n
%
GCS 15/“alert” GCS 12-15/“verbal”/“drowsy”/“rousable” GCS 8-11/“agitated”/“snoring”/“sedated”/“pain”/“asleep” GCS < 8/intubated/“deeply sedated”/“paralyzed + sedated” Not recorded
55 37 14 4 0
50 33.6 12.7 3.6 0
GCS 15/“alert” GCS 12-15/“verbal”/“drowsy”/“rousable”/“dozing”/“RASS-1” etc GCS 8-11/“Agitated”/“Snoring”/“Sedated”/“Pain”/“Asleep” GCS < 8/intubated/“deeply sedated”/“paralyzed + sedated” Not recorded
42 41 13 4 10
38.2 37.3 11.8 3.6 9.1
GCS = Glagow Coma Scale; RASS = Richmond Agitation-Sedation Scale; RFDS = Royal Flying Doctor Service.
when a Mental Health Act Form 3 (transport order) is in place.5 An RFDS flight is doctor accompanied when the assessing RFDS doctor deems this to be appropriate. A flight is usually doctor accompanied when the patient is unpredictable, has required significant sedation, or is perceived to pose a risk of in-flight violence. Patients are periodically reassessed in order to guide flight staffing and management. The rate of doctor-accompanied flights has increased significantly from 14% in 2004 to 46% in this study (P < .0001). This is further evidence to support Stokes’10 impression that mental health patients have become more challenging to manage in recent years. The management of an agitated or excessively sedated patient in flight is challenging, and this review revealed at least 1 patient when having an RFDS doctor on board would have been advantageous. Two near misses in which a doctor was on board for a second patient but was required for intervention were also noted. The 2 incidents of violence involved the same patient, a 13year-old Aboriginal/Torres Strait Islander male for involuntary mental health admission. The patient was initially assessed as suitable for nurse-only transfer with police escort but remained violent and agitated despite additional sedation. He was deemed to have become unsafe for air travel during airplane taxi and was returned to the
referring hospital. The patient was subsequently transferred the next day with a doctor, nurse, and police escort; however, he was still spitting at staff and needed additional sedation in flight. The majority of patients transferred by RFDSWO either required no in-flight sedation (53.6%) or no greater than midazolam 10 mg and/or haloperidol 10 mg without other agents (78%). Having a doctor on board was associated with a trend of receiving more in-flight benzodiazepines; however, once intubated transfers were excluded, this fell short of statistical significance (P = .06). This may be explained by better identification of patients likely to require inflight sedation; however, care should be taken to ensure that having a doctor on board does not lead to an expectation of deeper sedation. No statistically significant differences were found for inflight sedation given by sex, ethnicity, or history of substance misuse. This contrasts with indigenous patients receiving statistically greater doses of benzodiazepines and antipsychotics at referring centers. In flight, a variety of medications were used in patients who had agitation refractory to RFDS standard agents (midazolam, haloperidol, and diazepam). These included promethazine, propofol, and ketamine. Propofol (50-110 mg) was used in 4 patients; however, 1 patient became obtunded and required the use of an oropharyngeal airway. Le Cong et al11 studied the use of ketamine by bolus
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Table 7 Incidents Identified on Case Notes Review Incident
Demographic
Transfer Details
Preflight Sedation
In-flight Sedation
DR/NO
Details of Incident
Sedation
40 M non-ATSI
Derby-Broome 166 km
Midazolam 5 mg, diazepam 5 mg, clozapine 20 mg
Midazolam 1 mg, propofol 50 mg
DR
Prescription
55 F non-ATSI
Geraldton-Perth 370 km
Quetiapine 600 mg, diazepam (NR)
Midazolam 2 mg, haloperidol 10 mg
NO
Sedation (drug toxicity)
34 M ATSI
Nickol Bay–Broome 647 km
Midazolam 44 mg, haloperidol 5 mg, chlorpromazine 600 mg, diazepam 5 mg
Midazolam 19 mg, haloperidol 10 mg, promethazine 50 mg, propofol 50 mg
DR
Intubated transfer
34 M ATSI
Broome-Perth 1,683 km
As above
DR
Sedation
25 M non-ATSI
Nickol Bay–Perth 1,250 km
Staffing/sedation (drug toxicity)
35 M ATSI
Geraldton-Perth 370 km
Midazolam 36 mg, haloperidol 10 mg, olanzapine 10 mg, clonazepam 6 mg, propofol 100 mg Midazolam 100.5 mg, haloperidol 30 mg, olanzapine 10 mg, clonazepam 2 mg
Morphine 60 mg and midazolam 60-mg infusion Midazolam 6 mg, haloperidol 2.5 mg
Reduced GCS postsedation on aircraft, needed OP airway, was noted to be partially obstructing airway with sedation at referring location Inadequate anticipatory sedation prescribed, additional sedation prescribed after discussion with ground-based RFDS doctor Very agitated at referring location, commenced on chlorpromazine infusion. Still agitated in flight, required sedation ++, became tachypnoea, and saturations decreased. Antibiotics given for possible aspiration/pneumonia. Taken to Broome (planned mental health admission) where intubated in view of likely iatrogenic chlorpromazine overdose after discussion with toxicology. Ventilated transfer of above patient
Staffing
20 F ATSI
Port Hedland–Perth 1,323 km
Sedation
61 M non-ATSI
Prescription
DR
Noted difficult to sedate at referring hospital. Destination changed to emergency department in view of sedation.
None
NO
Midazolam 2 mg, olanzapine 10 mg, diazepam (NR)
Midazolam 5.5 mg, Haloperidol 10.5 mg, ketamine 200 mg
DR
Nickol Bay–Port Hedland 190 km
Diazepam 20 mg
Midazolam 10 mg, haloperidol 2.5 mg
DR
16 M non-ATSI
Geraldton-Bentley 380 km
Lorazepam 1 mg
Midazolam 15 mg
NO
Sedation (drug toxicity)
32 M non-ATSI
Port Hedland–Perth 1,323 km
Midazolam 15 mg, diazepam 20 mg, ketamine 750 mg (100 mg/h infusion)
DR
Staffing/sedation
52 M ATSI
Geraldton-Perth 370 km
Midazolam 17.5 mg, haloperidol 10 mg, olanzapine 30 mg, diazepam 10 mg, ketamine 490 mg (100 mg/hour infusion) Midazolam 127.5 mg, olanzapine 10 mg, diazepam 60 mg, clonazepam 10.5 mg, droperidol 12 mg
None
DR
Intubated transfer
30 F ATSI
Broome-Perth 1,683 km
Morphine 42 mg, midazolam 42-mg infusion
DR
High preflight sedation required. Flight nurse noted slightly prolonged QTc (.458 seconds) and exceeded daily haloperidol (discussed with Graylands). Patient known to have had previous episode of mental illness with ventilated transfer. Flight was uneventful but doctor-accompanied may have been more appropriate. No doctor assessed as required on flight (doctor was on for second patient). Patient agitated in flight; ketamine given for sedation. Sedation exceeded initial prescription for NO flight. Delirium in the context of alcohol withdrawal syndrome. Dropped GCS with sedation in flight; needed jaw thrust, nasopharyngeal airway, and flumazenil. Waited 5 days at referring center for bed to become available. Acute dystonia with IM zuclopenthixol. Was felt to be settled before transfer but became agitated and additional prescription from ground-based RFDS doctor was required. Reportedly difficult to sedate at referring hospital. Ketamine doses discussed with toxicology, felt potential for ketamine toxicity as exceeded maximum daily dose. Destination changed to QEII MC Emergency Department. GCS 5 when picked up by RFDS. Doctor on flight for second patient (this patient assessed as suitable for nurse only). Multiple high doses of different benzodiazepines. GCS 6 at end of transfer; taken to emergency department. Intubated at referring unit as agitated despite sedation. Problematic bronchospasm and oliguria during flight.
Midazolam 35 mg, clonazepam 1 mg, droperidol 10 mg
ATSI = Aboriginal/Torres Strait Islander; DR = doctor; F = female; GCS = Glasgow Coma Scale; IM = intramuscular; M = male; NO = nurse only; NR = not reported; RFDS = Royal Flying Doctor Service. Intubated transfer of patient with tonic-clonic seizure and desvenlafaxine overdose not felt to be a clinical incident as management appropriate (included in study because of coding as suicide attempt).
and, if required, a titrated infusion in 18 patients with acute agitation who did not respond adequately to first-line benzodiazepines and/or antipsychotics. Effective sedation for air medical evacuation was demonstrated without major adverse events. Ketamine was
used in 7 (6.3%) patients in this study under the direct supervision of an RFDSWO doctor. Six patients received bolus ketamine with a total dose range of 30 to 200 mg (mean = 114 mg) without adverse incidents. One patient had a ketamine infusion commenced
B. Wilkinson et al. / Air Medical Journal 37 (2018) 115–119
(100 mg/h [1 mg·kg·h−1]) at the referring hospital, receiving a total dose of 490 mg preflight. The patient remained agitated, and the infusion was continued in flight at the same rate, with additional ketamine given by bolus. The patient received 1240 mg ketamine in total. Refractory agitation was discussed with the state toxicology service, who felt that the patient demonstrated toxicity. Ketamine may have potential as a second-line agent for RFDS in Western Australia; however, the long journey times could lead to dose accumulation so additional study is warranted. The centrally acting alpha-agonists dexmedetomidine and clonidine have gained popularity for sedation in critically ill patients12 because of a reduction in delirium versus benzodiazepines13 and may also warrant further evaluation in the setting of air medical mental health transportation. The optimal depth of sedation for air medical transfer is an alert, calm, and cooperative patient; however, this can be difficult to achieve in patients with significant psychotic symptoms. The sedation should neither be so deep that it places the patient at risk of airway compromise nor so light that the patient is distressed by the experience or distresses other patients on board. One issue RFDS faces is the lack of on-board toilet facilities for restrained patients, and urinary catheters can be invaluable in ensuring patient comfort and prevention of urinary retention. There exists a cohort of patients (< 10%) who demonstrate tolerance and/or resistance to large doses of sedative medication. In-flight incidents demonstrate the challenges of preflight assessment and optimizing sedation. Unfortunately, it was impossible to determine with certainty the conscious level of patients at the start and the end of the period of RFDS care. Wide interindividual variation in reporting consciousness and agitation was present. The majority of patients had a safe conscious level; however, around 1 in 10 patients had a conscious level that risked airway compromise. Level of consciousness at the end of the transfer was similar to pretransfer consciousness. RFDSWO plans to implement the Richmond Agitation-Sedation Scale14 originally developed to qualify sedation depth in the intensive care unit as a means to standardize the reporting of consciousness and sedation in patients with acute psychiatric illness. Half of the transferred patients were accepted into a unit that did not have an emergency department and three quarters to a unit without an on-site intensive care unit. These units have limited capacity to manage patients who have received significant sedation. Future planning of inpatient mental health units should consider the provision of a monitoring facility for sedated patients. The current model for patients who have required significant sedation is assessment in an emergency department after flight; however, this has significant resource and patient flow implications. This study is limited by its retrospective design, and nonrecorded actions cannot be included. There also appears to be greater heterogeneity in this sample, with a lower rate of involuntary patients than Langford’s study.4 Nonetheless, the low rate of excluded
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patients is suggestive that this study represents the cohort of patients with acute mental ill health transferred by RFDS in Western Australia. Conclusions Despite the challenges of transporting acutely agitated patients over large distances, the rate of in-flight violence remained low. The majority of patients transferred in this study did not require large doses of in-flight sedation. A small number of patients required agents for refractory agitation, and deleterious effects of sedative medication were observed. The value of appropriate assessment, preflight sedation, mechanical restraint, and police escort supporting quality in-flight nursing and medical care should not be underestimated. Acknowledgment Mrs. Helen Bartholomew, Database Administrator, RFDS (Western Operations), Jandakot, for their help and work with database searches and records retrieval. References 1. Jones D. Aeromedical transportation of psychiatric patients: historical review and present management. Aviat Space Environ Med. 1980;51:709–716. 2. Flaherty T. Evacuation of wounded air from the battle of Guadalcanal. All Hands Naval Bulletin. 1942;306:2–6. 3. Western Australia Department of Health. Transport of Patients with Disturbed Behaviour from Country Hospitals to Perth. Department of Health and Allied Services Circular. 1983. Available at: http://www.health.wa.gov.au/ circularsnew/pdfs/5712.pdf. Accessed October 3, 2017. 4. Air transport of psychiatric patients in Western Australia. Available at: https:// www.health.wa.gov.au/publications/review/chapters/mental_health_3.7.pdf. Accessed October 3, 2017. 5. Government of Western Australia. Mental Health Act 2014 (MHA 2014). Office of the Chief Psychiatrist. Available at: http://www.chiefpsychiatrist.wa.gov.au. Accessed October 3, 2017. 6. Centers for Disease Control and Prevention. International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). Available at: http:// www.cdc.gov/nchs/about/otheract/icd9/abticd9.Htm. Accessed December 16, 2004. 7. McKnight PE, Najab J. Mann-Whitney U test. In: Corsini Encyclopedia of Psychology. 2010. 8. Upton GJ. Fisher’s exact test. J R Stat Soc Ser A. 1992;155:395–402. 9. Latt N, Conigrove K, Saunders JB, Marshall EJ, Nutt D. Addiction Medicine (Oxford Specialist Handbooks). Oxford, UK: Oxford University Press; 2009. 10. Stokes BA. Review of the admission or referral to and the discharge and transfer practices of public mental health facilities/services in Western Australia. Available at: https://www.mhc.wa.gov.au/media/1288/mental-health-review-report -by-professor-bryant-stokes-am-1.pdf. Accessed October 3, 2017. 11. Le Cong M, Gynther B, Hunter E, Schuller P. Ketamine sedation for patients with acute agitation and psychiatric illness requiring aeromedical retrieval. Emerg Med J. 2012;29:335–337. 12. Pichot C, Ghignone M, Quintin L. Dexmedetomidine and clonidine: from second-to first-line sedative agents in the critical care setting? J Intensive Care Med. 2012;27:219–237. 13. Riker RR, Shehabi Y, Bokesch PM, et al. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA. 2009;301:489–499. 14. Ely EW, Truman B, Shintani A, et al. Monitoring sedation status over time in ICU patients: reliability and validity of the Richmond Agitation-Sedation Scale (RASS). JAMA. 2003;289:2983–2991.