TY - JOUR
AU1 - USA, Nicole Powell-Dunford, MC
AU2 - RAMC, Alaistair Bushby,
AB - ABSTRACT Introduction: Sea sickness may greatly impact the readiness of Service personnel deployed aboard naval vessels. Medications used in the treatment of sea sickness may have adverse effects, limiting their use as flight crew. Although the prevalence of sea sickness in flight crews remains unclear, individual susceptibility and high sea states are established risk factors. Literature review can guide optimized management strategies for this population. Materials and Methods: The first author conducted a PubMed search using the terms “sea sickness” “flight crew” “scopolamine,” “hyoscine,” and “cinnarizine,” identifying 15 articles of 350 matches, which addressed potential impact to flight performance. Analysis also included two historic reports about motion sickness maintained within the U.K. Army Aviation Centre's aeromedical archives in Middle Wallop, Hampshire. Both authors reviewed aeromedical policy for the International Civil Aviation Organization, U.K. Civil Aviation Authority, U.S. Federal Aviation Authority, the National Aeronautics Space Administration, U.S. Army, U.S. Navy, and U.S. Air Force. Results: Scopolamine, also known as hyoscine, has fewer operationally relevant side effects than cinnarizine or first-generation antihistamines. Although no aeromedical authorities endorse the unsupervised use of scopolamine, many will consider authorizing its temporary use following an initial assessment on the ground. Evidence supports the concomitant use of stimulant medication for augmenting antinausea effects and countering the potential sedative effects of scopolamine. Conclusions: Scopolamine should be considered as a first-line medication for flight crews at risk of sea sickness but such use must be guided by the appropriate aeromedical authority, ideally in conjunction with a ground trial to evaluate individual response. The limited evidence to support concurrent use of stimulants must be weighed against the challenges of maintaining accountability of controlled substances in the operational environment. INTRODUCTION Authors have described motion sickness during naval operations since the time of ancient Greece.1 Even mild degrees of sea sickness can significantly impact multiple aspects of performance.2 Historically, military populations have used scopolamine (hyoscine), cinnarizine, and first-generation antihistamines to treat sea sickness3,–8 with the most recent operational research specifically evaluating scopolamine and cinnarizine4,9,–16 rather than the first-generation antihistamine medication class, now well established as causing problematic sedation.3,17,–20 Since the birth of naval aviation on November 14, 1910, when Ely's Curtiss Pusher aircraft launched from light cruiser USS Birmingham,21 many air crews have been exposed to naval flight deck operations along a continuum of risk for sea sickness—from days of extended duty during a high sea state to an isolated rapid refueling aboard a massive and stable aircraft carrier platform. Health care providers contemplating the use of sea sickness medications in flight crews must not only consider the operational setting but also consider the impact of sea sickness and sea sickness medications on human performance. The detrimental cognitive effects from either sea sickness or medication side effects could prove especially devastating in this occupational cohort. Two predominant theories of motion sickness currently exist. The hypothesis of sensory conflict postulates that motion sickness is caused by a mismatch between the current pattern of sensory inputs about self-movement and the pattern that is expected on the basis of previous experience. The hypothesis of postural instability theory postulates that motion sickness is caused by loss of postural control. There is presently more evidence for the sensory conflict theory, with researchers also hypothesizing contributory roles for visceral afference, thermoregulation, neuroendocrine, and epigenetic modulation factors.22,23 First-generation antihistamines such as diphenhydramine carry an unacceptable risk of somnolence and are prohibited for use in flight crew.5,–8,24,25 Cinnarizine is an atypical antihistamine with calcium channel blocking abilities used in the treatment of motion sickness, vertigo, and Meniere's disease; it is thought to work by interfering with the signal transmission between the vestibular apparatus of the inner ear and the vomiting center of the hypothalamus by limiting the activity of the vestibular hair cells.26 Although not available for prescription in the United States, cinnarizine has been used extensively by the British Royal Navy. Scopolamine is a competitive antagonist at muscarinic acetylcholine receptors and is used extensively for the prevention and treatment of motion sickness. Scopolamine works by acting on the maculae of the utricle and saccule. Some providers may prescribe concomitant stimulant medications to counter potential performance decrements associated with antinausea medication use. This focused literature review was undertaken in an effort to identify optimal sea sickness medication(s) for flight crews. To date, no studies have assessed the actual use of sea sickness medication in aircrew with ship board duties. However, this focused literature review may help elucidate the optimal sea sickness medications in this occupational cohort, filling a gap in current operational knowledge. METHODS Literature from several sources was reviewed between August 2016 and December 2016. The first author conducted a systemic PubMed search using the terms sea sickness, flight crew, scopolamine, hyoscine, and cinnarizine, identifying 15 articles from 350 matches which addressed potential impact of these medications on flight performance. The term sea sickness rather than motion sickness was used to identify literature most relevant to the research topic. First-generation antihistamines and meclizine were not included as part of the medication search terms because of their established lack of suitability in flight crews per current military aeromedical policies. Because of the small number of studies obtained through the search, none were excluded on the basis of publication date. Articles describing concurrent assessment of other medications apart from scopolamine and cinnarizine were not excluded from analysis. Review also included two historic reports about motion sickness maintained within the U.K. Army Aviation Centre's aeromedical archives in Middle Wallop, Hampshire. Both authors reviewed aeromedical policy for the British Army, U.K. Civil Aviation Authority (CAA), U.S. Federal Aviation Authority (FAA), the National Aeronautics Space Administration (NASA), U.S. Army, U.S. Navy, and U.S. Air Force. RESULTS Consistent good-quality patient-oriented evidence supports scopolamine as a first-line medication for preventing motion sickness for individuals who wish to maintain wakefulness, with inconsistent and/or limited quality patient-oriented research, substantiating the use of a first-generation antihistamine as an alternative.27,Table I outlines the basic pharmacologic properties of the scopolamine patch, a mode of delivery used in the management of sea sickness. In the most comprehensive analysis of scopolamine trials, 14 studies enrolling 1,025 subjects were reviewed. Evidence comparing the effectiveness of scopolamine to cinnarizine or combinations of scopolamine and ephedrine is equivocal or minimal. No evidence exists for the use of scopolamine alone or in combination with any other medication for the treatment of established motion sickness symptoms.16 The absorption and excretion of scopolamine varies greatly among individuals, with up to six-fold variation in patch users and a three-fold variation in oral users.27 TABLE I. Scopolamine Patch Information28 Dosage  Administration  Storage  Adverse Reactions  Withdrawal Symptoms  Idiosyncratic Reactions (Rare)  1.5 mg formulated to deliver approximately 1 mg of scopolamine over 3 days  Apply to the hairless area behind one ear at least 4 hours before exposure  20–25°C (68–77°F)  Two-thirds may experience dry mouth  Abrupt removal may cause dizziness, nausea, vomiting, abdominal cramps, sweating, headache, mental confusion, muscle weakness, slow heart rate, and low blood pressure  Acute toxic psychosis, including confusion, agitation, speech disorder, hallucinations, paranoia, and delusions    Wash hands with soap and water after application and removal to avoid ocular contamination    Less than 20% experience sedation      Dosage  Administration  Storage  Adverse Reactions  Withdrawal Symptoms  Idiosyncratic Reactions (Rare)  1.5 mg formulated to deliver approximately 1 mg of scopolamine over 3 days  Apply to the hairless area behind one ear at least 4 hours before exposure  20–25°C (68–77°F)  Two-thirds may experience dry mouth  Abrupt removal may cause dizziness, nausea, vomiting, abdominal cramps, sweating, headache, mental confusion, muscle weakness, slow heart rate, and low blood pressure  Acute toxic psychosis, including confusion, agitation, speech disorder, hallucinations, paranoia, and delusions    Wash hands with soap and water after application and removal to avoid ocular contamination    Less than 20% experience sedation      t1 Patch is common mode for scopolamine in the management of motion sickness. View Large TABLE I. Scopolamine Patch Information28 Dosage  Administration  Storage  Adverse Reactions  Withdrawal Symptoms  Idiosyncratic Reactions (Rare)  1.5 mg formulated to deliver approximately 1 mg of scopolamine over 3 days  Apply to the hairless area behind one ear at least 4 hours before exposure  20–25°C (68–77°F)  Two-thirds may experience dry mouth  Abrupt removal may cause dizziness, nausea, vomiting, abdominal cramps, sweating, headache, mental confusion, muscle weakness, slow heart rate, and low blood pressure  Acute toxic psychosis, including confusion, agitation, speech disorder, hallucinations, paranoia, and delusions    Wash hands with soap and water after application and removal to avoid ocular contamination    Less than 20% experience sedation      Dosage  Administration  Storage  Adverse Reactions  Withdrawal Symptoms  Idiosyncratic Reactions (Rare)  1.5 mg formulated to deliver approximately 1 mg of scopolamine over 3 days  Apply to the hairless area behind one ear at least 4 hours before exposure  20–25°C (68–77°F)  Two-thirds may experience dry mouth  Abrupt removal may cause dizziness, nausea, vomiting, abdominal cramps, sweating, headache, mental confusion, muscle weakness, slow heart rate, and low blood pressure  Acute toxic psychosis, including confusion, agitation, speech disorder, hallucinations, paranoia, and delusions    Wash hands with soap and water after application and removal to avoid ocular contamination    Less than 20% experience sedation      t1 Patch is common mode for scopolamine in the management of motion sickness. View Large Diverse motion sickness delivery systems and operationally relevant performance impacts are described within the literature. A review of transdermal scopolamine commissioned by the U.K. Institute of Aviation Medicine determined that the scopolamine patch's slow drug release enables effective blood levels to be maintained for 72 hours, with minimization of side effects; however, the patch requires 6 to 8 hours for effectiveness and can be associated with visual blurring when worn over 24 hours, especially in hypermetropes.9 Mydriasis resulting from ocular contamination through a finger has been reported.15 A study conducted at the German Air Force Institute of Aviation Medicine determined that scopolamine nasal spray was effective and safe for the treatment of motion sickness with a fast onset of action (within 30 minutes) and with no signs of nasal or epipharyngeal irritation.10 Several operationally oriented studies have assessed performance impact of seasickness medication. A British analysis of six sea trials predating 1990 determined transdermal scopolamine to be superior to 50 mg dimenhydrinate for the control of sea sickness, with most significant antinausea effects appreciated during early days at sea, before adaptation to the motion of the ship has occurred.9 The Israel Naval Institute has undertaken the largest of these studies, initially publishing results from a randomized double-blind, placebo-controlled cross-over study in 2001. In this trial, researchers assessed the objective performance and self-reported well-being of 60 young naval crew in the comparison of a single 100 mg dose of dimenhydrinate, a single 50 mg dose of cinnarizine, and a single transdermal scopolamine patch. Although dimenhydrinate was associated with performance decrements and decreased well-being, neither the cinnarizine nor the transdermal scopolamine impacted performance or reported well-being. Dry mouth was the only adverse effect reported by the sailors, in association with scopolamine use.3 In a sea trial published in 2012, the Israel Naval Medical Institute compared a 1.5 mg transdermal scopolamine patch with 25 mg cinnarizine pills through a double-blind, randomized, cross-over study of 76 navy crew on two deployments. Subjects reported the scopolamine patch to be significantly more effective than the cinnarizine tablet and attributed a “moderate-to-high” degree of drowsiness more frequently to cinnarizine (34%) than to the scopolamine patch (17%). Subjects reported side effects more frequently with cinnarizine (38%) than with the scopolamine patch (22%); comparison with placebo was only of borderline significance. A significantly greater percentage of subjects preferred transdermal scopolamine to cinnarizine.4 A U.K. Royal Navy survey assessed 12 adult males in a double-blind cross-over study comparing 0.6 mg scopolamine to 30 mg cinnarizine, each administered three times a day. Both medications significantly impacted memory and four-choice reaction time without impact on mood. Repeated doses of scopolamine led to increasingly distant near point convergence values, which were not clinically significant.13 In a smaller study involving six men, British researchers conducted a placebo-controlled, double-blind, cross-over design assessment of the sedative effects of cinnarizine using 10 mg promethazine as a control. 15 mg doses of cinnarizine did not impact performance but were associated with sleepiness at 5 hours. 30 mg and 4 mg doses significantly impacted performance at 5 hours.12 Some medical providers use sea sickness medications in combination with stimulants, given the improvements in reaction times, vigilance, and learning noted in adult males taking stimulant medication.29 In a 1968 study, Wood et al noted that six different combinations of motion sickness medications and stimulants achieved an increased tolerance for head movements associated with motion compared to scopolamine monotherapy, with scopolamine delivered in doses from 0.3 to 1.2 mg.19 Other studies demonstrate that codelivery of scopolamine 1 mg and 1.2 mg in combination with 10 mg dexedrine is superior compared to delivery of scopolamine 1 mg alone in terms of tolerance for motion.18 In 1985, Wood et al assessed various motion sickness and stimulant medication combinations in a series of trials involving 10 subjects. Delivery of 1 mg doses of scopolamine in conjunction with 10 mg amphetamine was associated with significant performance improvement compared to baseline performance on a computerized tracking test with good operational correlation. Lower doses of amphetamine, delivered independently or in conjunction with a variety of motion sickness medications, were not able to raise computerized performance scores above baseline. Doses of 0.8 mg and 1.0 mg scopolamine significantly reduced subject performance on computerized tracking, as did 25 mg doses of promethazine delivered through either the IM or oral route.20 In a small trial published in 1988, researchers from Massachusetts Institute of Technology determined that eight subjects treated with 0.4 mg oral scopolamine and 5.0 mg oral dextroamphetamine did not experience any decrements in Symbol-Digit Substitution, Simple Reaction Time, Pattern Recognition, Digit Span Memory, and Pattern Memory, although noting that higher doses of either medication have been reported to be associated with performance decrements in earlier studies.14 Estrada et al evaluated various motion sickness medications in healthy nonaviator male passengers exposed to turbulent helicopter flight, specifically evaluating the use of 25 mg of promethazine in combination with 200 mg caffeine, 25 mg meclizine, a 1.5 mg scopolamine patch, an acustimulation wristband and placebo in four groups of 16 subjects, respectively. Each subject participated twice—once with a treatment and once with placebo. Only the promethazine and caffeine combination group showed a statistically significant reduction in nausea and motion sickness severity, and an improvement in reaction time when compared with its placebo control.17 NASA's reduced gravity program assessed oral Scop/Dex (0.4 mg scopolamine/5 mg dexedrine) to be free from operationally visual side effects; this medication causes dry mouth as well as nonclinically significant changes in pupil size and near point accommodation with no decrement in visual acuity.11 The most recent study assessing combinations of motion sickness and stimulants determined that the efficacy of scopolamine with modafinil (1 + 10 mg/kg) was equivalent to that of scopolamine with d-amphetamine (1 + 1 mg/kg).30 Military and civil aeromedical authorities provide diverging guidance regarding the management of motion sickness; neither provides specific guidance for the management of sea sickness as an environmentally specific condition. Most aeromedical authorities take a case by case approach with a temporary authorization of specific motion sickness medication(s). U.S. commercial pilots currently require FAA approval to use medication for motion sickness.25 The U.S. Army permits pilots to use promethazine (Phenergan) 25 mg combined with ephedrine 25 mg or L-scopolamine hydrobromide alone or in combination with dextroamphetamine (Scop/Dex) for up to three flights during training or for reacclimation provided the pilot is accompanied by an instructor pilot with no waiver requirement.7 The U.S. Navy does not consider motion sickness to be disqualifying in student aviators when it is transient, resolving spontaneously or when addressed according to specific Chief of Naval Air Training Instruction. Ginger, 250 mg up to 1 g, may be taken by U.S. Navy flight crew members before situations where motion sickness may be an issue without waiver requirement; however, dosage cannot exceed a total of 4 g daily.8 In the U.S. Air Force, airsickness requiring pharmacologic therapy beyond the service's established Airsickness Management Program is disqualifying and not eligible for waiver. Approved medications, when used as part of this program, include transdermal scopolamine 0.5 mg/dextroamphetamine sulfate 5 mg (Scop/Dex patch), given 1 to 2 hours before flight for three consecutive flights for one flight per day. Flight surgeons can consider scopolamine hydrobromide 0.45 mg in 15 mL of elixir with dextroamphetamine sulfate 7.5 mg, or other approved medications as alternatives.5 The U.K. civil aviation authority considers aeromedical examiner directed use of cinnarizine or cyclizine for the prevention of motion sickness provided 2 days of initial use on the ground and the absence of any sedation with use.24 The U.K. Royal Air Force Manual—Assessment of Medical Fitness (2016) states that hyoscine hydrobromide or cinnarizine is normally only prescribed for limited periods to aircrew in training. Because of potential side effects, pilots using such medications are unfit for solo flying and must fly with a pilot suitably qualified on type.6 DISCUSSION Well-established variations in individual responses to scopolamine as well as a range of doses and delivery options may account for differences in side effects, reported well-being, and performance in various antimotion sickness trials. The preponderance of evidence suggests that scopolamine is the first-line medication for those who need to preserve optimum performance in an operational environment, with cinnarizine as an alternative, which is clearly superior to first-generation antihistamines. Clinicians should realize that some important side effects may occur in therapeutic doses of scopolamine. Evaluating individual response to specific dose and delivery mode is a prudent aeromedical policy. An imperfect therapeutic approach has resulted in notable variations in civil and military aeromedical policy for the management of motion sickness. Some evidence supports the use of stimulant medication, as delivered concurrently, to scopolamine to counter what may be subtle performance decrements. However, controlled substances require special handling and storage considerations as they present a risk of diversion and misuse. Benefits of concurrent administration of caffeine rather than a scheduled drug include reduced risk for abuse, reduced risk for psychotic reaction, and a reduction in the logistical constraints of obtaining and storing a controlled substance. Benefits of caffeine stimulation must be weighed against diuretic effects, especially in the hot weather environment. The use of a combination of caffeine and scopolamine has not been studied but could afford operational benefit. There are several limitations to this review and its usefulness in its application to military flight crews. To date, studies have mostly assessed the performance impact of sea sickness medications in healthy males in the absence of provocative stimuli, using computerized performance assessments rather than observation of assigned operational duties. Furthermore, the aeromedical policy review was limited to U.K. and U.S. aeromedical authorities. Further exploration of other military aeromedical policy may provide further insights regarding the administration of sea sickness medications to flight crews. Comprehensive international aeromedical policy review was beyond the scope of this review. Importantly, the magnitude and duration of exposure to a provocative environment may vary considerably across shipboard-deployed air crew members, requiring a nuanced approach to the prevention and management of sea sickness. For the long-term deployment of aircrew aboard naval vessels, individuals with known sensitivity to sea sickness should be proactively managed. A brief refueling sortie on a large aircraft carrier would probably have negligible impact on aircrew, whereas patient movement associated with a delay in takeoff secondary to recovery of medical equipment and/or nonpermissive departure conditions may provoke sea sickness, especially in a nonhabituated crew landing aboard a small vessel in a high sea state. In these instances, contingency availability of medications could prove useful but timing their administration is problematic as the greatest benefit requires treatment before symptoms have begun. CONCLUSION Although the use of motion sickness in aircrew with duties aboard navy ships has not been formally assessed, pertinent literature supports the use of scopolamine and/or scopolamine-stimulant combination medications for those with a known predisposition toward motion sickness while aboard ships. The requirement for special handling and storage of controlled substances makes scopolamine without concurrent administration of a stimulant medication the easiest motion sickness medication to use. Further research regarding the incidence of sea sickness in embarked flight crews can help better inform this problem. REFERENCES 1. Hippocrates. Aphorisms 4, sec 14. 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TI - Management of Sea Sickness in Susceptible Flight Crews
JF - Military Medicine
DO - 10.7205/MILMED-D-17-00029
DA - 2017-11-01
UR - https://www.deepdyve.com/lp/oxford-university-press/management-of-sea-sickness-in-susceptible-flight-crews-hUgciPaV9R
SP - e1846
EP - e1850
VL - 182
IS - 11
DP - DeepDyve
ER -