Seasickness susceptibility and the vestibular time constant: a prospective study.

Human passive motion during boat, car or airplane travel may trigger motion sickness. Seasickness is the most provoking manifestation of motion sickness. It imposes major constraints on quality of life and human performance. Based on seasickness susceptibility the population is usually categorized into susceptible (S) and non-susceptible (NS). During repeated exposure some susceptible individuals undergo habituation and obtain symptoms relief, reflecting a third group of habituating (H) individuals. Recently, accumulative evidence suggests that the vestibular time constant (Tc) is associated with motion sickness susceptibility and attenuation of symptoms. These studies demonstrated that repeated passive motion stimuli lead to temporary short-term (days) changes in Tc, whereas sea sickness habituation process lasts 3 to 6 months. Therefore, the goal of the present study was to examine the behavior of Tc during the entire span of the seasickness habituation process between the H, S and NS groups to find an objective test for seasickness severity prediction. Tc of 30 subjects was prospectively evaluated pre, 3 and 6 months post exposure to sea environment using a computerized rotatory chair system protocol. Seasickness severity was evaluated by Wiker questionnaire. Significantly shorter Tc was found in the S group compared with the NS and H groups. Further analysis revealed lower maximal Slow Phase Velocity (mSPV) and nystagmus frequency (total number of beats/second) in the S group. Our results suggest that Tc, mSPV and nystagmus frequency might serve as a prediction for seasickness severity. This study was retrospectively registered on December 7th 2022 and assigned the identifier number NCT05640258.

The Vestibular Time Constant and Clinical Response to Antimotion Sickness Medication.

OBJECTIVE: The therapeutic effects of antimotion sickness medications involve suppression of several components along the vestibular system. Scopolamine-based medications have proved to be the most effective anti-seasickness agents. However, there is high variability in individual responses. The vestibular nuclei, in which the vestibular time constant is modulated, contain acetylcholine receptors which are affected by scopolamine. The hypothesis of the study was that successful seasickness prevention by scopolamine requires vestibular suppression to be reflected by the shortening of the vestibular time constant. DESIGN: Subjects were 30 naval crew members suffering from severe seasickness and were treated with oral scopolamine. The study participants were defined as responsive or non-responsive to the anti-seasickness medication according to the clinical outcome: successful response to scopolamine was defined as a reduction of seasickness severity from the highest score of 7 according to the Wiker scale to 4 or less. Scopolamine and placebo were assigned to each subject in a crossover, double-blind design. The horizontal semicircular canal time constant was evaluated by a computerized rotatory chair before, 1 and 2 hours after drug or placebo administration. RESULTS: The vestibular time constant was significantly shortened from 16.01 ± 3.43 seconds to 12.55 ± 2.40 seconds ( p < 0.001) in the scopolamine-responsive group but not in the nonresponsive group. In contrast, vestibular time constant values were 13.73 ± 4.08 and 12.89 ± 4.48 for baseline and 2 hours measurements, respectively. This change was not statistically significant. CONCLUSIONS: Reduction in the vestibular time constant after scopolamine administration can be used to predict whether motion sickness alleviation will occur. This will enable the administration of appropriate pharmaceutical treatment without the need for prior exposure to sea conditions.

Galvanic vestibular stimulation as a novel treatment for seasickness.

Motion sickness is the cause of major physical discomfort and impaired performance in many susceptible individuals. Some habituate to sea conditions, whereas others remain chronically susceptible, requiring lifelong pharmaceutical treatment. The present study sets out to investigate whether galvanic vestibular stimulation (GVS) coupled with rotatory chair stimulation could mimic sea conditions and alleviate motion sickness symptoms in individuals deemed chronically susceptible. Thirty seasickness susceptible subjects, after at least six months of regular sailing, were enrolled in a prospective, single-blind, randomised controlled study. The treatment group underwent GVS coupled with inverse phase rotatory chair impulse in sinusoidal harmonic acceleration protocol. The control group underwent a sham procedure. All subjects performed repeated velocity step tests to determine the vestibular time constant (Tc) and completed a seasickness questionnaire. The GVS rotatory chair procedure decreased the prevalence of severe seasickness. The number of motion sickness clinic visits and anti-motion sickness drug consumption were reduced in the treatment group three-month post intervention as compared to control. In addition, there was significant reduction of Tc in the treatment group. GVS coupled with rotatory chair impulse could decrease motion sickness severity, induce neurophysiological learning processes and promote habituation to seasickness in chronic susceptible subjects. This is a novel and promising non-pharmacological method to treat motion sickness susceptible individuals. Furthermore, the investigation demonstrated that adaptation to sea conditions may take place even after years of susceptibility to seasickness. This study was retrospectively registered on August 10th 2021 and assigned the identifier number NCT05004818.

Long-term scopolamine treatment and dental caries.

OBJECTIVES: To investigate whether scopolamine, an anticholinergic agent which induces hyposalivation, represents a risk factor for the occurrence of dental caries. MATERIALS AND METHODS: A retrospective cohort study was carried out among sailors treated with scopolamine for seasickness. The study population included 370 young healthy male adults (18-30 years old) who served in the Israel Navy between 2012 and 2016. Of these, 66 subjects who were chronically treated with intermittent administration of scopolamine, either by the oral or transdermal route, were assigned to the study group. Documented subject characteristics included age, socioeconomic status, level of education, body mass index, smoking history, and dental hygiene. Follow-up lasted 1 to 3.5 years. RESULTS: Two- to 3.5-year follow-up revealed a higher risk of dental caries in 15 of 16 subjects (93.8%) treated with an average of 50.9 mg scopolamine, in contrast to only 71 of 108 control subjects (65.7%) (RR = 1.43, p = 0.02 [95% CI = 1.18-1.72]). Follow-up for 1-1.5 years revealed a lower occurrence of dental caries in both the study group (11/22, 50.0%) and the control group (46/104, 44.2%). Follow-up of 1.5-2 years also revealed less dental caries, in 16/28 subjects (57.1%) in the study group and 51/92 subjects (55.4%) in the control group. The differences were not statistically significant. CONCLUSIONS: In healthy young adults, prolonged intermittent use of scopolamine was found to be a risk factor for the development of dental caries. CLINICAL SIGNIFICANCE: Dental care and hygiene should be intensified when administering hyposalivatory anticholinergic agents.

Evidence for the initiation of decompression sickness by exposure to intense underwater sound.

Mass stranding of cetaceans (whales and dolphins), in close association with the activity of naval sonar systems, has been reported on numerous occasions. Necropsy showed bubble-associated lesions similar to those described in human decompression sickness (DCS). We examined the hypothesis that exposure to underwater sound may potentiate DCS. Rats were subjected to immersion and simulated dives with and without simultaneous acoustic transmissions at pressure levels and frequencies of 204 dB/8 kHz and 183.3 dB/15 kHz. DCS severity was assessed using the rotating wheel method. Recording of somatosensory evoked potentials (SSEPs) was employed under general anesthesia as an electrophysiological measure of neurologic insult. A significantly higher rate of decompression sickness was found among animals exposed to the 204-dB/8-kHz sound field. Significantly higher pathological SSEPs scores were noted for both underwater sound protocols. Pathological SSEPs scores in animals immersed during the acoustic transmissions, but without changes in ambient pressure, were comparable to those observed in animals exposed to the dive profile. The results demonstrate induction of neurological damage by intense underwater sound during immersion, with a further deleterious effect when this was combined with decompression stress. The study outcome has potential implications for human diving safety and may provide an explanation for the mass stranding of cetaceans purportedly associated with sonar activity.

Medical waiver for flying after microvascular decompression for hemifacial spasm.

BACKGROUND: Microvascular decompression has become the treatment of choice for hemifacial spasm. Post-surgical symptoms of vestibular dysfunction may appear, but are mostly transient. The unique occupational demands of military aviators necessitate complete otoneurological evaluation after vestibular insults to allow safe return to flying duties. CASE REPORT: We present a case of a military jet-fighter pilot who developed transient vertigo and disequilibrium after microvascular decompression for hemifacial spasm. Resolution of symptoms and complete recovery as documented by vestibular bedside and laboratory tests allowed us to grant the pilot full solo flying privileges.

Monothermal caloric testing in the screening of vestibular function.

INTRODUCTION: The alternate binaural bithermal caloric test (ABBT) is the standard test for evaluation of the dizzy patient. Monothermal caloric testing (MT) has the potential benefits of reducing the administration time and patient discomfort. The goal of the present study was to investigate the role of MT screening in the prediction of ABBT results. METHODS: ABBT results of 218 patients having normal otoneurological examination, normal hearing, and normal electronystagmography (ENG) were retrospectively analyzed to generate norms for all subtests. These norms were then employed to calculate the sensitivity and specificity of MT for predicting normal ABBT in a group of 197 consecutive dizzy patients who were referred for vestibular testing. RESULTS: The best predictions of ABBT by MT results were achieved when ENG testing showed oculomotor integrity and no spontaneous, positional, or positioning nystagmus. Under these conditions, warm MT lateralization < 32% had 90% sensitivity and 92% specificity for the prediction of normal ABBT. DISCUSSION: When no pathology is detected in the other parts of the ENG, warm MT lateralization < 32% can indicate normal ABBT with a 10% probability for a false-negative result. This false negative rate precludes the routine use of warm MT in the clinical realm and its application as a screening tool for possible vestibular deficits in a generally healthy population like aviation or diving candidates. Higher sensitivity may be achieved by lowering the cut-off point of the response asymmetry required for the diagnosis of MT screening failure and the omission of directional preponderance diagnosis from the goals of the screening.

Vestibular evoked myogenic potentials and saccular plasticity in divers.

INTRODUCTION: Otolith function, which is dependent on linear velocity and acceleration, may be expected to change in underwater divers, who are submerged in a medium that is denser than air. The purpose of the present study was to examine possible changes in the sacculocollic reflex of professional divers and to investigate whether there might be diving-induced adaptation of the saccular response. METHODS: We used the vestibular evoked myogenic potential (VEMP) response to evaluate saccular function in 12 professional divers shortly after a dive and after an interval of at least 24 h. The control group consisted of 12 matched non-divers. Wave latencies and amplitudes, asymmetry ratio, and the response threshold were compared between the groups. RESULTS: Statistically significant shortening of N23-wave latency was found in the divers compared with the control group. The mean +/- SE were 22 +/- 0.1 and 22.1 +/- 0.7 ms early and late after a dive in the divers group vs. 24.5 +/- 0.5 ms in the control group. No significant differences were found in any of theVEMP parameters between the early and late post-dive recordings. DISCUSSION: We suggest that the reduction in N23 latency reflects long-term adaptation of the sacculocollic reflex to underwater conditions. Increased sensitivity of the reflex is required to compensate for the decrease in linear velocity and acceleration, resulting in reduced stimulation of the otolith organ.

Scopolamine Treatment and Adaptation to Airsickness.

BACKGROUND: Airsickness is a clinical syndrome manifesting in a variety of symptoms, particularly nausea and vomiting during flight. Studies of habituation to motion sickness in humans treated by scopolamine have produced conflicting results. The drug accelerated habituation, but a rebound effect on symptom severity was observed after its withdrawal. The purpose of the present study was to investigate whether scopolamine affects the adaptation process. We also evaluated the relationship between initial symptom severity and adaptation to airsickness.METHODS: Aviator cadets in the first two stages of their training were divided into two groups, treated and not treated by scopolamine. Airsickness severity was evaluated using both simulator sickness and motion sickness questionnaires, and drug administration was recorded.RESULTS: A statistically significant higher rate of adaptation was observed among the scopolamine-treated group compared with the nontreated group. On the simulator sickness questionnaire, rate of adaptation for the two groups was -0.21 ± 0.53 and -0.1 ± 0.17, respectively, and for the motion sickness questionnaire -2.34 ± 1.54 and -0.91 ± 1.41, respectively. Examination of a possible connection between initial symptom severity and adaptation rate failed to reveal a significant relationship.CONCLUSIONS: We recommend the use of oral scopolamine to accelerate habituation and find it a relatively safe short-term treatment for airsickness. Our results support the notion that scopolamine accelerates the natural adaptation process.Doron O, Samuel O, Karfunkel-Doron D, Tal D. Scopolamine treatment and adaptation to airsickness. Aerosp Med Hum Perform. 2020; 91(4):313-317.

Ondansetron for the prevention of seasickness in susceptible sailors: an evaluation at sea.

BACKGROUND: Seasickness is a common problem, causing a significant decrement in performance among naval crew. In about 20-60% of crewmembers, symptoms appear with varying intensity depending on the sea state and the duration of the voyage. Recent studies have suggested antiemetic 5HT3 blockers as a possible treatment for motion sickness, emphasizing their minor clinical and cognitive side effects. The purpose of the present study was to evaluate the 5HT3 blocker ondansetron in the prevention of seasickness. METHODS: There were 16 volunteers with a normal otoneurologic examination and no previous medical history of inner ear disease or vertigo who took part in a double blind, randomized, crossover study. During an initial learning phase, the participants practiced on a battery of computerized performance tests until their results stabilized. Ondansetron 8 mg or placebo was administered 2 h before sailing aboard a 500-ton naval vessel in mild sea conditions. Participants did the performance tests and completed a questionnaire evaluating their seasickness symptoms 4 h into the voyage. RESULTS: No statistically significant reduction of seasickness symptoms was demonstrated between ondansetron treatment and placebo (a Wiker score of 2.69 +/- 1.78 and 2.81 +/- 1.97, respectively). There was no statistically significant difference in side effects or the results of the performance tests. CONCLUSION: In this study, ondansetron was not found to be beneficial in the treatment of seasickness. It could be speculated that the mechanism of nausea in seasickness is different from that of toxin-induced nausea.

Otoacoustic emissions in early noise-induced hearing loss.

OBJECTIVE: To follow changes in transient evoked and distortion product otoacoustic emissions (TEOAEs, DPOAEs) as they relate to pure-tone audiometry (PTaud) thresholds during the first 2 years of occupational noise exposure. DESIGN: Prospective controlled. METHODS: Pure-tone audiometry thresholds, TEOAE and DPOAE amplitudes, and contralateral medial olivocochlear reflex strength were repeatedly evaluated during 2 years and compared between and within a cohort of 135 ship engine room recruits and a control group of 100 subjects with no noise exposure. RESULTS: Pure-tone audiometry thresholds for 2,000, 3,000 and 4,000 Hz in both ears were significantly elevated in the study group after 2 years of noise exposure. Significantly lower TEOAE amplitudes were found at 2,000 Hz in the right ear and 2,000 and 4,000 Hz in the left ear. Longitudinal intrasubject analysis of the study group revealed significant reductions of TEOAE amplitudes at 2,000 to 4,000 Hz in both ears and reduced DPOAE amplitudes for 5,957 Hz in the right ear and 3,809, 4,736, and 5,957 Hz in the left ear in the second follow-up evaluation. Baseline medial olivocochlear reflex strength showed no correlation to PTaud thresholds after 2 years of noise exposure. Poor to moderate negative linear correlations (r = -0.07 to -0.37) were found between the DPOAE-averaged amplitudes at 2,979 to 5,957 Hz and PTaud threshold means at 3,000 to 6,000 Hz. Abnormal TEOAE parameters after the first year of noise exposure had high sensitivity (86-88%) and low specificity (33-35%) for the prediction of noise-induced hearing loss (NIHL) after 2 years. CONCLUSION: The DP-gram is not significantly correlated with PTaud and cannot be used as an objective measure of pure-tone thresholds in early NIHL. Medial olivocochlear reflex strength before the beginning of chronic exposure to occupational noise has no relation to individual vulnerability to NIHL. Although TEOAEs changes after 1 year showed high sensitivity in predicting NIHL after 2 years of exposure, they cannot be recommended as an efficient screening tool due to high false-positive rates.

Seasickness pathogenesis and the otolithic organs: vestibular evoked myogenic potentials study--preliminary results.

BACKGROUND: Seasickness is thought to result from conflicting inputs from the vestibular, visual and somatosensory systems. The otolithic organs, which are responsible for the sensation of linear acceleration and tilt, are important in the pathogenesis of seasickness. The vestibular evoked myogenic potentials test is an objective evaluation of saccular function. OBJECTIVE: To examine whether saccular function is related to the pathogenesis of seasickness. METHODS: VEMP was performed in 10 subjects susceptible to seasickness and in 14 non-susceptible subjects. RESULTS: Bilateral VEMP responses were obtained in 7 (50%) of the non-susceptible subjects and 1 (10%) of the susceptible subjects. No differences were found between the groups in P13 and N23 wave latencies, amplitudes, N13-P23 inter-peak latencies, and peak-to-peak asymmetry ratios. More subjects in the susceptible group had asymmetry ratios > 35%. CONCLUSIONS: The attenuated saccular response might be explained in the context of the neural-mismatch theory and/or the subjective vertical theory, as reflecting an adaptation effort to sea conditions. A larger study is necessary to determine whether a statistically significant difference in VEMP responses exists between seasickness-susceptible and non-susceptible subjects.

Vestibular Derangement and Motion Intolerance in VATER Association.

VATER association is a nonrandom occurrence of congenital malformations: vertebral defects, anal atresia, tracheoesophageal fistula, renal defects, and radial bone anomalies. We report the case of a 19-year-old man with a childhood diagnosis of VATER association, who presented to the motion sickness clinic with severe seasickness. We discuss the clinical and laboratory diagnosis of vestibular pathophysiology, which was confirmed by MRI of lateral semicircular canal and vestibule dysplasia. We suggest the possibility of vestibular involvement as part of the developmental field defect associated with VATER syndrome, which hitherto has rarely been reported.

Vestibular evoked myogenic potential threshold and seasickness susceptibility.

Numerous attempts have been made to find physiological parameters that might predict susceptibility to seasickness. However, to date, no physiological index has been found that can serve as a diagnostic tool for individual susceptibility to motion sickness at the personnel selection stage. A number of studies have demonstrated that linear acceleration in the vertical plane is the most provocative stimulus of motion sickness. The main physiological sensory modality responsible for monitoring vertical acceleration is the saccule. Over the last decade, vestibular evoked myogenic potentials (VEMP) have come to be recognized as a reliable procedure for the evaluation of saccular function. We used the VEMP test to assess otolith responses in 15 seasickness-susceptible (SS) and 15 non-seasickness-susceptible (NSS) healthy male crew members. The SS group exhibited a significantly higher VEMP threshold and a significantly lower peak-to-peak p13-n23 amplitude interval compared with the NSS group. Further analysis by logistic regression found threshold to be the dominant factor associated with seasickness susceptibility. The study demonstrated differences in the VEMP reflex of the SS and NSS groups. The threshold difference may represent an intrinsic mechanistic difference between the vestibular systems of the two groups. Theoretically, increased susceptibility to seasickness may be due to a discrepancy between the various neural systems as a result of reduced otolith responses.

CO2 detection in closed-circuit oxygen divers with and without a distracting task.

INTRODUCTION: Elevated arterial PCO2 (hypercapnia) increases the risk of CNS oxygen toxicity when diving with enriched oxygen gas mixtures. A CO2 detection and retention test is conducted as a matter of routine at the Israel Naval Medical Institute for physiological training, and as a screening tool for divers who may be prone to suffer from CNS oxygen toxicity. This test does not include an "attention distracter", which would provide a better simulation of the true situation during actual diving. The purpose of the present study was to examine the hypothesis that the addition of cognitive tasks to the CO2 detection and retention test might alter divers' detection ability. METHODS: We assessed ventilatory and perceptual responses to variations in inspired CO2 (range 0-5.6 kPa, 0-42 mmHg) during moderate exercise, with and without the addition of cognitive tasks, in 15 Israel Navy combat divers on active duty. The first stage was the CO2 detection training session, followed by the CO2 detection test session (TEST) and the CO2 detection test session while doing cognitive tasks (COGN). The latter two sessions were performed by some of the subjects in reverse order. RESULTS: We found that the mean (+/- SD) PICO2 at the detection threshold was significantly lower in the COGN (1.7 +/- 0.8 kPa, 12.7 +/- 6.0 mmHg) than in the TEST (2.4 +/- 0.6 kPa, 18.1 +/- 4.5 mmHg). The mean PETCO2 while inspiring 5.6 kPa (42 mmHg) CO2 was not significantly different in the two tests. CONCLUSION: We suggest that the ability to detect CO2 during a dive is not impaired, but rather improves when the diver's attention is focused on other tasks.

Vestibular evoked myogenic potentials and motion sickness medications.

OBJECTIVE: Seasickness is a widespread problem among naval crew, and has a major impact on their performance at sea. The three pharmacological agents most commonly employed in the treatment of seasickness are dimenhydrinate, cinnarizine, and scopolamine. At present, the effectiveness of anti-seasickness drugs is tested by a process of "trial and error", while sailing and exposed to sea conditions. A physiological test to evaluate the action of a drug might save crew members long periods of suffering, as well as simplifying the procedure of selecting the appropriate treatment for each individual. The cervical vestibular evoked myogenic potentials (cVEMP) test has come to be recognized as a reliable procedure for the objective evaluation of saccular function. It was the hypothesis of the present study that cVEMP otolith responses may be affected by anti-motion sickness drugs, which might thus make cVEMP a useful clinical neurophysiological tool for the assessment of drug absorption and efficacy. METHODS: Thirty male sailors who regularly took medication for the treatment of seasickness participated in the study. Participants underwent the cVEMP test pre- and 1h post-drug administration. RESULTS: A statistically significant decrease in p13 latency was found after administration of scopolamine compared with baseline (14.46ms vs. 15.09ms, p=0.0049), with significant prolongation of the binaural average inter-latency in this group. No differences were found in the dimenhydrinate and cinnarizine study groups. CONCLUSIONS: This study demonstrated that scopolamine absorption can be verified by changes in cVEMP latencies. SIGNIFICANCE: The potential of the cVEMP test for predicting action of scopolamine on the vestibular system.

Electrophysiological modulation of cardiomyocytic tissue by transfected fibroblasts expressing potassium channels: a novel strategy to manipulate excitability.

BACKGROUND: Traditional pharmacological therapies aiming to modify the abnormal electrophysiological substrate underlying cardiac arrhythmias may be limited by their relatively low efficacy, global cardiac activity, and significant proarrhythmic effects. We suggest a new approach, in which transfected cellular grafts expressing various ionic channels may be used to manipulate the local electrophysiological properties of cardiac tissue. To examine the feasibility of this concept, we tested the hypothesis that transfected fibroblasts expressing the voltage-sensitive potassium channel Kv1.3 can modify the electrophysiological properties of cardiomyocytic cultures. METHODS AND RESULTS: A high-resolution multielectrode mapping technique was used to assess the electrophysiological and structural properties of primary cultures of neonatal rat ventricular myocytes. The transfected fibroblasts, added to the cardiomyocytic cultures, caused a significant effect on the conduction properties of the hybrid cultures. These changes were manifested by significant reduction in extracellular signal amplitude and by the appearance of multiple local conduction blocks. The location of all conduction blocks correlated with the spatial distribution of the transfected fibroblasts assessed by vital staining. All electrophysiological changes were reversed after the application of Charybdotoxin, a specific Kv1.3 blocker. In contrast, conduction remained uniform in the control hybrid cultures when nontransfected fibroblasts were used. CONCLUSIONS: Transfected fibroblasts are able to electrically couple with cardiac myocytes, causing a significant local and reversible modification of the tissue's electrophysiological properties. More broadly, this study suggests that transfected cellular grafts expressing various ionic channels may be used to modify cardiac excitability, providing a possible future novel cell therapy strategy.

Inner ear decompression sickness and mal de debarquement.

OBJECTIVE: To present a case series of vestibular symptoms appearing after combined sailing and diving activity, and to discuss the differential diagnosis and the workup algorithm. STUDY DESIGN: Case series. SETTING: Tertiary referral center. PATIENTS: Three patients aged 25 to 31 years suffering from unsteadiness and movement sensations after sailing and scuba diving. INTERVENTIONS: Neurotologic evaluation and recompression therapy in a hyperbaric chamber. MAIN OUTCOME MEASURES: The increasing popularity of marine sports and leisure activities has resulted in the exposure of a growing number of people to unique abnormalities not encountered under terrestrial conditions. The otolaryngologist who is involved in the care of these patients is required to diagnose and treat diving-related sinus and ear injuries such as barotrauma and decompression sickness, and also to be familiar with sailing-related disorientation syndromes such as seasickness and mal de debarquement. Treatment modalities for the various abnormalities differ significantly, and early commencement of treatment is often crucial for a successful outcome. CONCLUSION: Whenever doubt exists, recompression treatment must be instituted as soon as possible because of the potential for severe sequelae if the patient is left untreated, and because the risks involved in this therapy are minimal.

Scopolamine patch to prevent seasickness: clinical response vs. plasma concentration in sailors.

INTRODUCTION: Scopolamine is highly effective for the treatment of seasickness. Nevertheless, transdermal therapeutic system (TTS) scopolamine, despite high compliance on the part of persons treated by the drug, fails to provide protection against seasickness in 26-38% of patients. To the best of our knowledge, the correlation between scopolamine levels in plasma and its therapeutic effect under sailing conditions in the open sea is investigated for the first time in the present study. METHODS: Subjects were 61 crewmembers of naval vessels treated by TTS scopolamine. The therapeutic response at sea was documented by questionnaire. During a period ashore, a TTS scopolamine patch was applied in the same subjects. Blood samples were taken and an adverse effects questionnaire completed 8 h after scopolamine patch application. Scopolamine levels were determined using an established radio-receptor assay procedure. To verify the reproducibility of these measurements, blood samples were taken twice from most subjects, on separate days after different patch applications. Subjects were divided into "responders," who reported at least a moderate decrease in seasickness severity compared with their previous experience at sea without TTS scopolamine therapy, and "non-responders," who had only slight symptomatic relief or no relief at all. RESULTS: The mean scopolamine concentration in the plasma of the 37 responders (156.77 +/- 77.03 pg x ml(-1)) was significantly higher than the mean level in the 24 non-responders (97.03 +/- 73.34 pg x ml(-1); p = 0.005, simple t-test). CONCLUSIONS: Attempts to increase scopolamine levels in plasma by increasing the drug dosage or improving transdermal absorption should be considered for the treatment of "non-responders".

Airsickness: Etiology, Treatment, and Clinical Importance-A Review.

Airsickness is one of the forms of motion sickness, and is of significance in both commercial and military flight. Whereas commercial airline passengers may simply feel poorly, the effect of airsickness on military aircrew may lead to a decrement in performance and adversely affect the mission. This is of major importance in the case of flight safety, when a pilot who is incapacitated may endanger the aircraft. The problem is particularly evident in pilot training, because of the high incidence of airsickness at this stage in the pilot's career. The majority of aircrew undergo habituation to airsickness during their service, with a reduction in symptoms and improved function. Although airsickness is a wellknown problem in aviation, we were unable to locate a review of this topic in the literature. This review focuses on the characteristics, clinical evaluation, and treatment of airsickness. It also presents the experience of the Israeli flight academy, and our solution for Navy pilots who have to contend with the risk of seasickness before taking to the air.