Textbook of Maritime Medicine

Seasickness is a common phenomenon on board of seagoing ships, and it may affect a significant percentage of crew and passengers, particularly in heavy weather and when sailing in high seas. It may be regarded as the prototypic and most widely recognized form of motion sickness and it has been a nemesis of seafaring ever since man first dared to take out to sea in dugout canoes. Up to date seasickness seldomly is being understood as a potentially serious medical condition and people affected are rather getting mocked than pitied, since it is reversible and recovery usually is swift. Still seasickness is treacherous when seriously impacting on the mental and physical performance of professionals or when progressing into a crisis after sustained vomiting and fluid loss. This may imply social, technical and procedural consequences, in particular relating to the safety of navigation. In today´s shipping crew headcount is decreased to the minimum required and the (functional) loss of a significant number of crew due to seasickness may well impact on the navigation and overall safety of a ship. This holds true for yachtsmen as well, who in contrast to professional sailors often lack routine, regular training and exposure towards heavy weather. In severe weather conditions all hands of small vessel crews are needed, however a significant proportion may simply not be able to leave their bunks due to seasickness. The additional strain put on the remaining active crew puts them at risk of getting tired which in turn renders them more susceptible to seasickness. Apart from these navigational and safety related implications, seasickness may in some cases also have serious medical relevance, for instance if psychosis develops and the affected individual tries to jump over board, or if a diabetic patient becomes hypoglycemic. Motion sickness may also aggravate loss of body heat in immersion, thereby promoting hypothermia and reducing survival times in naval accidents [[1]; [2]].

10.13.1 Epidemiology of seasickness

The incidence and prevalence of kinetosis has been investigated in particular in space aviation, among marines and seafarers, as well as in yacht crews taking part in offshore races. Regarding motion sickness on seagoing vessels it is obvious that wind force and sea condition largely contribute to the incidence. About one third of passengers on ferries do on average experience motion sickness symptoms of various degrees [[3]]. A ship´s size, its hull shape, the speed and course of movement in relation to the environment (wave direction, length and amplitude, wind direction and force) largely determine the level of motion stress for the individual [[4] ]. People aboard of small vessels are particularly prone to become seasick, since a small craft tends to inflict more motion stress upon its passengers than a large ship in similar weather and sea conditions. Still a substantial percentage of passengers being unaccustomed to the sea may experience motion sickness even on a tall cruise ship mildly rolling along in a moderate Atlantic swell. There also is no absolute resistance found against motion sickness, thus even professional and fully habituated crews of large container ships and oil tankers may become seasick in stormy weather and high seas. Experience from very severe sea conditions including reports of life raft passengers actually indicates that given sufficiently provocative circumstances almost anybody will eventually get seasick [[5]].

10.13.2 Etiology and pathogenesis

It has been stated that motion sickness is a normal reaction to an abnormal environment. In essence motion sickness is caused by exposure to complex, passive, and most often three-dimensional movements of the body in different vessels or environments such as cars, busses, trains, ships, airplanes, funfair rides or space travel. Noteworthy even mere visual immersion into a virtual reality environment without any body movement may cause motion sickness symptoms, though full blown sickness is rarely seen in such settings.

The most nauseogenic movements are [ [6]]:

• heave (up-and-down, elevator-like) motions,
• rolling around the longitudinal axis,
• yawing around the transversal axis,
• and pitching around the transversal axis,

Apparently these different motion components may potentiate each other´s nauseogenic impact significantly, a condition which rather is the rule than the exception when being at sea. In consequence a stimulus well above the individual threshold for motion sickness may be generated.

The complex accelerations and decelerations as well as changes in the gravitational axis associated with these motions are being perceived by the equilibrium organ (esp. otoliths in the labyrinth) and proprioreceptors in muscles and tendons, however they often cannot be matched with appropriate visual information. This is the case for instance in a ship cabin, where the passenger´s body feels the ship´s movements, however the cabin walls will remain static to the subject´s visual senses. But even if the passenger has a window to look out of, the reason for the acute movements will not be obvious in most instances, in particular on large ships.

This situation is addressed by the leading etiological hypothesis of motion sickness, called the „sensory mismatch theory“, alluding to conflicting sensory input as the major trigger of motion sickness. Visual system and vestibular system are predominant providers of postural information, however their relative importance may vary inter-individually. In subjects with impaired vestibular function the visual system may partially take over maintenance of postural control [[7]]. 

In contrast, the modified „subjective vertical conflict theory“ postulates the importance of the >true< (gravitational) vertical axis for individual posture and balance. According to this hypothesis motion sickness is triggered by divergence between the plumb-line expected on the basis of formerly experienced patterns and the actual „real“ plumb line generated by sensory afferent impulses [[8]]. No matter which of those hypothesis comes closest to truth, a functioning vestibular system is an essential prerequisite for inducing motion sickness [5].

Further to the pathogenesis, afferent information in particular on posture and movements is sent to the brain stem from different sources including visual system, vestibular system, muscular proprioceptors, cochlea, cortex, limbic system, olfactory system and the intestine (esp. stomach via N. vagus). The sensory mismatch perceived by the brain triggers seemingly dysfunctional vegetative actions (vestibulosympathetic reflex), typically associated with motion sickness. This causes a stimulation of the emesis center located in the formatio reticularis, thus preparing to coordinate a potential subsequent act of vomiting

Fig. 10.13.1 Central processing of afferences by the formatio reticularis (emesis center) in the brainstem. Nauseogenic information from the labyrinth (histaminergic afferences on posture, acceleration), the stomach (Nervus vagus, serotoninergic afferences), the limbic system (triggered by e.g. fear, disgust), and the chemo-triggerzone (dopamine- and opioid-receptors) are being received, weighed and in case of sufficient stimulus, retching and vomiting is initiated and coordinated. D2= Dopamine; H1= Histamine; M= Acetylcholine; 5-HT3= Serotonine (adapted from: Heintze K. Pharmaka mit Wirkung auf den Gastrointestinaltrakt. In: Estler CJ (Ed.). Pharmakologie und Toxikologie. 5. Aufl. Stuttgart, New York: Schattauer 2000). 

In motion sickness alterations in gastric wave patterns may be detected via electrogastrograms (EGGs), typically found shifted towards tachygastria (3.6-9.9 cpm), or mixed tachy- and bradygastria (1.0-2.4 cpm) [[9];[10];[11]]. In essence this >gastric arrhythmia< precludes a normal, coordinated propulsion of stomach content towards the duodenum and the distal GI tract, thereby increasing stomach distension and contributing significantly to nausea and vomiting.

Cardiovascular reactions comprise a short-lived increase in blood-pressure (up to 10 mmHg), probably mediated via epinephrine, and tachycardia. An increase in peripheral blood flow (forearm) seems to be inversely correlated with resilience towards motions sickness [[12]]. Further down the line blood pressure usually decreases to hypotonic levels [[13]], which may be more pronounced in case of emesis-related fluid loss. An enhanced vasopressin (ADH) secretion in the motion sick has been observed by multiple investigators [11;[14];[15]]. Its relevance is supported by the observation of tachygastria and nausea being induced by experimental vasopressin administration [[16]]. Individuals with increased resilience towards motion sickness stimuli also seem to generate lower vasopressin levels [[17]]. One may speculate on the physiological function of vasopressin increase as a potential means to counterbalance the anticipated or imminent loss of fluid and electrolytes (via emesis), aiming at maintaining blood pressure via reduced diuresis.

Further observations of endocrine changes include increases in ACTH and ß-endorphines [17].

 As to the individual disposition some factors contributing to susceptibility for seasickness have been identified. People of Asian descent have a markedly reduced threshold (by –50% -65%) for experiencing symptoms of seasickness. This is in line with motion sickness tests demonstrating that Asian volunteers experience a higher intensity of nausea, and higher vasopressin levels compared to Caucasians, suggesting a genetic susceptibility to vection-induced motion sickness and nausea [11;[18]]. Thus seafaring Asian nations such as ancient China have sought for remedies for this „curse of navigation“, coming up with some usable approaches such as ginger root ingestion and acupressure.

Female gender also seems to enhance motion sickness susceptibility, and some fluctuation of susceptibility has been observed with the menstrual cycle [[19]]. Migraine may also increase sensitivity to motion stimuli and recent findings indicate that depletion of tryptophane, the serotonine precursor found in food such as egg, fish or cheese, may aggravate motion sickness susceptibility both in migraineurs as well as in healthy controls. This suggests that serotonine depletion may be an important factor in migraine and may as well facilitate motion sickness [19;[20]].

Schoolchildren experience an increased sensitivity to motion sickness that peaks around the age of 11 years for girls and as late as 21 years for male adolescents [[21]]. Patterns of postural stability acquired and refined throughout childhood and adolescence may not match with the afferent postural and labyrinthic impulses when at sea [[22]]. Conversely newborns and toddlers are resistant to motion sickness which fits well with their usual situation of being carried around by their parents [[23]]. Ageing plays a positive role as motion sickness susceptibility usually decreases with age and even gender differences are eventually levelling [21].

Golding et al. have devised a motion sickness susceptibility questionnaire (MSSQ-Short), which may serve to assess an individual´s proneness to become motion sick in reference to average benchmarks and percentiles. Past (childhood) motion sickness experience has a strong impact on the overall score. Apart from research purposes this questionnaire can be useful when assessing crew or advising travellers on prophylactic measures before boarding a cruise ship [[24]]: http://www.westminster.ac.uk/__data/assets/pdf_file/0010/47539/MSSQ-short.pdf )

The MSSQ has also been found the best predictor for test-induced motion sickness, even exceeding ethnic and gender-related influences [18].

Further variables may often have decisive impact on induction and intensity of motion sickness:

• Psychological factors such as an increased level of anxiety [[25]], situation related anxiety (i.e. fear of flying, fear of the sea), mistrust or sensations of helplessness
• Unpleasant smells (i.e. vomit, toilet, diesel fuel)
• Time of day (increased sensitivity at night due to tiredness and the lack of compensational optical afferences, in particular the horizon)
• Tiring and exhaustion are rather strong co-factors that may significantly reduce the threshold for motion sickness
• Lack of habituation (“getting one´s sea legs”) before strong stimuli occur (e.g. gale, high seas or swell), particularly during the start phase of a cruise
• Alcohol may persist in the vestibular endolymphatic fluid for more than 24 hours and moderate to heavy alcohol intake may even lead to a loss of already acquired habituation

It remains enigmatic as to why motion stimuli may actually make people sick and helpless, instead of causing swift habituation or - at the other extreme - a „fight or flight“ adrenergic emergency reaction. Despite the high level of research conducted, the riddle of a potential physiology or utility behind motion sickness remains to be solved. Maybe this truly unpleasant syndrome is good for some purpose? One recent hypothesis postulates that the sensory mismatch as experienced in motion sickness may actually mimic an acute ingestion of toxins. This sounds convincing because intoxication and motion sickness are sharing symptoms such as nausea, vertigo and retching. Intoxication has been a serious threat throughout evolution of mankind, and triggering elimination of potentially lethal toxins via reduction of gastric propulsion and emesis may be considered a life-saving reflex [[26]]. This theory would also match with the age maximum observed in adolescents, being known for taking high risks and at the same time being comparatively inexperienced.

10.13.3 Clinical symptoms

Motion sickness almost invariably presents as a syndrome, comprising multiple symptoms (Table 10.13 1, Figure 10.13 2). Initially signs of discomfort such as epigastric sensations, mild dyspepsia, headache (predominantly frontal), drowsiness, tiredness, yawning, shivering, cold sweating, hot flashes, pallor, increased salivation, strangury (painful urination) and lacrimation may precede outright motion sickness (malaise). The complex of drowsiness and mood changes seen in motion exposed persons has also been named >Sopite syndrome< [[27]].

Characteristic neuromotor symptoms are swaying, poor coordination, tremble and muscular weakness [[28]], effects putting sailors at an increased risk of injury, falling, and submersion.

Gastrointestinal manifestations include loss of appetite, gulping, nausea and vomiting, but may also comprise bowel movements.

Fig. 10.13.2 Pathophysiology and symptomatology of motion sickness. Sensory input from different sources may trigger and modulate motion sickness, which may manifest in an great variety of symptoms in multiple organ systems involved. Vegetative, gastrointestinal and neurological symptoms are commonly recognized by motion sickness patients. (Adapted from: Wolffgram T. Motion- and seasickness (Kinetosis) – Update on pathophysiology, prophylaxis and therapy. Medizinische Welt 2000;132: 21-27)

Impact on mental function may be discrete at onset with reticence, low mood, fatigue, malaise, decreased vigilance and low level of concentration, the latter being supported by impaired performance in psychometric testing including reduced short term memory [[29]]. More advanced symptoms comprise increasing indifference, vertigo and visual disturbances. Aggravation towards apathy with severely impaired decision-making capabilities is seen in severely affected subjects. On rare occasions mental impairment may proceed until loss of conscience or delirium.

Even moderate impact on decision-making capabilities may already lead to faulty navigation and poor vehicle guidance by crews of seagoing vessels, potentially facilitating accidents and major average. The skipper or captain of a ship should diligently take this >human factorall hands on deck<.

In severe motion sickness repeated vomiting and associated fluid loss may occur. If not compensated by fluid and electrolyte substitution, this may result in hypotonic dehydration and metabolic alkalosis, further adding to the malaise and rendering the patient apathetic and weak Furthermore vomiting may also contribute to a loss of body heat. Due to impaired vasoconstriction and thermoregulation seasick sailors immersed in cold water are significantly more prone to core cooling [1;2], which may reduce their survival time. Therefore motion sickness remedies should be given to sailors in due time, e.g. before embarking on a life raft or a survival craft (TEMPSC) ( see 10.13.4 Prophylaxis and 10.13.5 Treatment).

A diagnostic scale for the assessment of motion sickness has been devised first by Graybiel et al. [[30]], predominantly accounting for gastrointestinal symptoms occuring at different stages of the condition. The Graybiel scale (Table 10.13.1a) assigns points to various symptoms ranging from mild accessory phenomena such as epigastric awareness (1 point), to severe nausea including retching or vomiting (16 points). The latter indicates full-blown motion sickness, whereas malaise is differentiated into four different grades ranging from mild (1-2 points) to severe (sum of points from 8 to 15 points).

Table 10.13.1a: Cardinal symptoms of motion sickness and criteria for grading motion sickness severity (Graybiel-Scale) [30]

 Severity: I= Slight, II= Moderate, III= Severe. AQS= Additional Qualifying Symptoms. Scores in the 8-15 points range indicate severe malaise.  

Further diagnostic scales for motion sickness assessment have been developed and validated since, including the MSAQ [[31]], which differentiates four different symptom groups (gastrointestinal, central, peripheral, and Sopite-related. Table 10.13. 1b). This approach captures mood-changes (annoyance, uneasyness) as well as drowsyness and fatigue (“Sopite syndrome”, sopire (lat.)-> to put to sleep; [[32]] http://en.wikipedia.org/wiki/Sopite_syndrome), thereby extending the range of relevant motion sickness symptoms when compared to the classic Graybiel Scale.

Table 10.13.1b: Motion Sickness Assessment Questionnaire (MSAQ). Courtesy Dr. Peter J. Gianaros, Pittsburgh [31] 

Instructions. Using the scale below, please rate how accurately the following statements describe your experience, where 1 = not at all and 9 = severely.

1. I felt sick to my stomach (G)

2. I felt faint-like (C)

3. I felt annoyed/irritated (S)

4. I felt sweaty (P)

5. I felt queasy (G)

6. I felt lightheaded (C)

7. I felt drowsy (S)

8. I felt clammy/cold sweat (P)

9. I felt disoriented (C)

10. I felt tired/fatigued (S)

11. I felt nauseated (G)

12. I felt hot/warm (P)

13. I felt dizzy (C)

14. I felt like I was spinning (C)

15. I felt as if I may vomit (G)

16. I felt uneasy (S)

Investigator use: G; Gastrointestinal; C: Central; P: Peripheral; SR; Sopite-related.

The overall motion sickness score is obtained by calculating the percentage of total points scored: (sum of points from all items/144) × 100. Subscale scores are obtained by calculating the percent of points scored within each factor: (sum of gastrointestinal items/36) × 100; (sum of central items/45) × 100; (sum of peripheral items/27) × 100; (sum of sopite-related items/36) × 100.

Being exposed to sea-motions while working or cruising on ships usually leads to habituation (adaptation) within 2-5 days, accompanied by a decline in symptoms in subjects prone to seasickness. Habituation may outlast the end of the cruise for a few weeks, however sleep deprivation or heavy alcohol consumption may increase motion sensitivity again at any given time.

Surprisingly, a good indicator for individual habituation to sea motion stimuli seems to be the sensation of a swaying type of vertigo, experienced not at sea but on dry land [[33]]. This phenomenon is harmless and usually ceases 1-2 days after the end of the journey, however rare cases of chronic vertigo have been reported after ocean cruises. This so called mal-de-debarquement-syndrome is observed mainly in middle-aged women and may prove refractory to pharmacotherapy and physiotherapy [[34]].

10.13.4 Impact on co-morbidities and drug absorption

Most importantly sea-sickness may also aggravate chronic illness, such as diabetes, chronic renal disease and other relevant medical conditions.

Table 10.13. 2: Motion sickness: Impact on Co-morbidities. These are just a few examples of relevant medical condition, essentially any chronic or acute disease requiring medication may become affected by severe motion sickness by loss of medication via vomit, irregular drug ingestion times, or altered pharmacokinetics.

Obviously vomiting poses an issue regarding loss of oral medication for acute and chronic diseases. Even low to medium grade motion sickness may impair gastrintestinal motility, resulting in an altered drug absorption, which may also put patients at risk of an insufficient medication. This is highly relevant in a number of conditions, e.g. in transplant patients depending on oral anti-rejection drugs. Severly seasick female passengers taking the pill may need to apply additional contraceptive measures for weeks until their subsequent menses.

10.13.5 Prophylaxis of seasickness

A variety of precautionary measures and fundamental rules may help to prevent or at least to curtail motion sickness manifestations in seafarers, such as:

• Alcohol and nicotine avoidance before and during travel
• Maintenance of sufficient sleep and recovery time
• Avoidance (already at planning) of nightly travels and cruises, especially at the beginning of the voyage; surely this is neither doable in cargo shipping nor on cruise ships with a tight schedule
• Choice of cabins with bull eyes/windows in the middle or rear section, close to sea level. If anxiety regarding seafaring is involved, a cabin well above sea level may be more appropriate
• Walking on deck at frequent intervals while fixing the horizon often is beneficial
• Reading for longer periods should be avoided
• One should not tilt the head forward unnecessarily
• Sufficiently warm (but not too warm), breathable clothing is important
• Good ventilation should be warranted, avoiding smell of e.g. diesel, toilets and cooking
• Regular fluid intake (non-alcoholic drinks) should be maintained
• Small meals at regular intervals, preferably proteins and carbohydrates, avoiding fatty meals and beverages with cream or fatty milk
• Positive thinking and the deliberate acceptance of the situation of being on a voyage
• Listening to favorite music (e.g. via MP3 player, iPod) may significantly improve the mood and may help to relieve anxiety
• Putting on acupressure wristbands at the Nei Guan-Point [[35]] may also prove beneficial (Figure 10.13.3) 
• Lying comfortably in a horizontal position with eyes closed
• Inquire about stabilizers when booking a ship cruise, older constructions may be more prone to rolling in high seas.
• When chartering or booking berths on sailing yachts, size surely matters: The bigger the yacht the better, at least in terms of nauseogenicity of ship motions.
• Sailing yacht hull shape influences motion patterns; yachts equipped with a heavy long keel show more steady motions compared to short-keelers. Wing-keels may favorably reduce heave motions.
• Catamarans in general usually put less motion stress on their passengers (exception: going against in high seas may lead to stressful >slamming
•  Sensitive individuals should definitely consider using a medication prophylaxis:
• Ginger-Tablets or preferably approx. 1-2 g fresh ginger root 2 hours prior to start of the voyage [[36]]. Putting sliced fresh ginger into hot tea (and chewing the bits afterwards) or between slices of bread makes it more pallable.
• In case of a heavy weather forecast or if the individual has experienced severe motion sickness before, highly reliable prophylactic medication such as scopolamine patches, meclizine supp. or dimenhydrinate supp. should be administered (Table 10.13. 3) in due time before departure.

 Motion-sensitive travelers often experience anticipatory anxiety in the beginning of a cruise. Relaxation exercises such as autogenic training, progressive muscle relaxation/PMR, and biofeedback may help to alleviate anxiety and thus help to prevent or at least curtail motion sickness symptoms.

Professional airspace training programs exposing astronauts´ heads to repeated accelerations and decelerations as well as turns and rotations, are achieving some level of subsequent tolerance to motion stimuli. Regularly performing sports in general seems to have a beneficial overall effect on motion sickness susceptibility, in particular sports training proprioception (Thai Chi, Judo, etc. [[37]]).

A diet low in histamine content (e.g. via avoidance of fish, cheese, tomatoes, chocolate etc.) has been proposed as a prophylactic measure [[38]]. This may indeed make sense in patients with proven deficiency of histamine degrading enzyme (Diaminoxydase, DAO), however no clinical proof has been provided in healthy sailors. This measure may even be detrimental, since some of the food quoted (cheese, chocolate, meat) also is a major source of tryptophane, and tryptophane ingestion may reduce susceptibility to motion sickness [20].

Recently a study by Greek investigators found an association between Helicobacter pylori eradication treatment of aviators and an increase in their motion stimuli tolerance (number of habituation flights), thus treating motion sensitive H.P.-positive personnel may provide an additional prophylactic measure [[39]].

An effective prophylaxis against seasickness is of utmost importance in case of distress at sea, in particular shipwrecking – as soon as possible before passengers and crew start to embark on rescue vessels such as life-rafts or totally-enclosed motor-propelled survival craft (TEMPSC). Given the extreme movements of a small raft in heavy seas even experienced sailors may get seriously seasick within a short period of time, making them prone to loss of fluid and putting them at an increased risk of going over board of the raft. Motion sickness may also aggravate loss of body heat in immersion, thereby promoting hypothermia and reducing survival times in naval accidents [1;2]. Therefore a scopolamine patch or a dimenhydrinate- or meclizine-suppository should be administered to each passenger in due time before entering a life-raft or rescue shuttle (as soon as the necessity to abandon ship becomes obvious). A recent publication [[40]] suggests that antihistamines such as dimenhydrinate may be more beneficial regarding core cooling than scopolamine, as shown in an experimental setting. However further evidence may be required before a specific advice can be given and a potential benefit may be set off by a lower responder rate to dimenhydrinate when compared to scopolamine. In general, practical survival training and good leadership seem to play a very important role in the amelioration of seasickness in such emergencies [[41]].

In case of full-blown motion sickness symptoms (moderate malaise A or worse, see table 10.13.1a) occurring early on despite precautionary measures, one should readily initiate appropriate treatment (always check for contraindications and caveats first) – (see 10.13.6 Treatment and Table 10.13. 3).  

10.13.6 Treatment of seasickness

As a prelude to this paragraph it needs to be mentioned that only a modest number of valid studies on remedies for seasickness has been conducted thus far. Unfavorably the intensity of current research activities lags behind the 1960ties and -70ties, when space motion sickness research was heavily funded by the US and Russian governments. Noteworthy a significant percentage of remedies used today are either not backed by controlled trials or they are supported by trials with a design not fully representative of real life sea-sickness conditions. This is the case for many clinical studies investigating anti-emetics in anaesthesia and oncology. Ondansetron for instance is effective in a chemotherapy and PONV (postoperative nausea and vomiting) setting, but it failed in a real life navigation trial [[42]]. Still data of a few nicely designed though small controlled studies are available (please refer to paragraphs on specific medications), some even including active comparator arms, and thus they may aid chosing the appropriate prophylactic or therapeutic medication. In general investigators also need to ackknowledge that the design of sea-sickness studies is strongly affected by intra-(day-to-day) and inter-individual variability in response to motion sickness stimuli, as well as a high level of placebo-responsiveness. And last but not least certain side affects of remedies investigated may even mimick some of the seasick symptoms such as drowsiness, headache, and vertigo.

There are also rather different policies and practices in the use of motion sickness remedies found in different countries and regions, thus the drug-of-choice in one country may even be banned or not registered at all in another country (e.g. the anti-histamine cinnarizine is popular in the UK, but banned in the US!).

Therapy should start as soon as possible after onset of first symptoms. Individuals with a known predisposition for motion sickness should be asked which remedies have worked in the past for them and how well they were tolerated. If not done yet motion-sick individuals should apply prophylactic measures described in 10.13.5. If feasible one ought to look at the horizon which may help to stabilise head posture and vestibular system in relation to vessel movements. Resting in supine position and closing the eyes usually improves or at least contains motion sickness symptoms [[43]].

Mildly motion-sick individuals on leisure sailing yachts or motor yachts should be offered to take the helm, however without fixing the compass for longer periods (surveillance of a qualified person/navigator is recommended anyhow). This often provides the affected person with a feeling of control over the vessel and the situation [ [44] ], furthermore reducing the sensory information conflict by anticipation of ship movements (waves are seen before they move the vessel). Complex tasks involving forced head inclination or reclination ought to be avoided. The head should be turned towards the direction of the most prominent vessel movement, for instance facing sidewards in case of heavy rolling, or towards the bow in case of intense pitching. A rather favorable resting place is within a hammock, which largely reduces the impact of rolling or pitching movements (depending on the axis of hammock installation).

 A relieving non-pharmacological remedy is manual acupressure of the so called Nei-Guan-Point (P6) (Figure 10.13. 3) at the volar side of the forearm approximately 3 fingertips proximal of the wrist fold the between the two most prominent flexor tendons [35]. Alternatively wrist-bands with pressure pads (motion sickness bands) may also be used at the same site, however pressure needs to be applied with caution to avoid tissue damage (interchanging wrist-bands between left and right arm is recommended). Anti-emetic efficacy of wristbands has also been shown in palliative care patients [ [45]], and a recent Cochrane Review concluded that there is evidence that P6-stimulation reduces risk of nausea and vomiting vs sham treatment in postoperative care [[46]]. An FDA-approved electro-stimulation device (ReliefBand®) was found to be efficacious both before and after start of anaesthetic treatment in patients of high risk of experiencing post-surgery nausea and vomiting [[47]]. An alternative acupressure point is K-K9 on the volar side of the middle phalanx of the 4^th finger [[48]].

Figure 10.13.3 a,b,c: Manual Acupressure of the Nei Kuan-Point (PC-6); a: The Nei Kuan Pont is located two thumbwidths cranial of the volar wrist skinfold between the two prominent flexor tendons. b: Gently press the Nei-Kuan-Point with the opposite hand´s thumb tip with slightly circulating and undulating motions for at least a minute, thereafter switch to the opposite arm. Repeat procedure regularly several times, as long as needed. c: Acupressure wristbands should be positioned similarly. (© Dr. Thomas Wolffgram, 2011)  

Pharmacotherapy of motion sickness comprises a variety of drug-classes with differing principles (Table 10.13. 3). In general caution is warranted when prescribing or administering motion sickness remedies, in particular with regards to children, to pregnant women, to the elderly or to persons with relevant co-morbidities ( also see table 10.13.3 and paragraph on “Pharmacotherapy (prophylaxis and treatment) of seasickness in specific populations” below).

The anticholinergic scopolamine (transdermal patches, tablets, nasal spray) is the among the most potent and reliable drugs for prophylaxis and treatment of motion sickness available [[49]]. However quite a few caveats and contraindications, in particular in the elderly have to be regarded (Table 10.13. 3), which renders this drug less popular among doctors on cruise ships, usually with a high percentage of elderly passengers on board. Special caution should be warranted in passengers with a medical history of glaucoma, restricted urinary flow (e.g. due to prostate adenoma), pylorus stenosis, cardiac arrhythmia, clincally relevant cerebral sclerosis or atopic dermatitis (Table 3). Despite its proven efficacy, about 26-38% of individuals fail to respond, probably due to low scopolamine plasma levels [[50]]. As a workaround for lack of efficacy and delay in onset of action (0.5- 4hrs, full plasma levels at 6 hrs) some studies have used transdermal scopolamine in combination with a single dose of oral scopolamine (0.3 mg or 0.6 mg [49]. Another trial investigated the utility and safety of double scopolamine patches in those sailors (age 18-21 years) who did not respond adequately to a standard single patch in first instance. The authors conclude that a double dose may safely administered (notably in the in young sailors investigated only) and increases the likelihood of efficacy by raising scopolamine plasma levels [[51]]. A recent study by Simmons et al. [[52]] shows the utility of intranasal scopolamine (INSCOP) in subjects prone to seasickness. The combination with amphetamines (e.g. d-amphetamine (=dexedrine) 5- 10 mg.) is considered superior by some investigators to scopolamine monotherapy [[53]], however legal restrictions for storage and use of amphetamines on ships have to be regarded. Scopolamine works via inhibition of both gastral tachyarrhythmia and vasopressin release, furthermore by reduction of the CNS neural mismatch signal (modifying neural store). Scopolamine also seems to facilitate the process of habituation regarding motion stimuli [[54]].

Seasickness per se may impair vigilance, performance of complex tasks and decision making. Most studies support the notion that scopolamine does not impair mental performance and conclude that individuals treated may safely handle a ship. However a reaction time increase vs. placebo has been observed in Swedish naval cadets in a simulation model [[55]]. Combination with amphetamines may potentially compensate these effects.

Table 10.13. 3: Stage-related treatment of motion sickness. Please always refer to the current prescription information or package leaflet first for all treatment aspects including dosing. Side effects, drug interactions and contraindications listed in this table are exemplary and may not be complete. In established motion sickness oral medication should be avoided (except liquid) and either suppositories or parenteral administration (i.v., i.m.) should be used if feasible.

• H(Histamine)1-receptor-antagonists have shown efficacy in motion sickness models [[56]] including reduction of symptoms and of gastric tachyarrhythmia, e.g.:
• Dimenhydrinate (tablets, suppositories, injectable; e.g. Dramamine®, Vomex®) is a salt consisting of diphenhydramine (H1-antagonist) and 8-chlorotheophylline (a stimulant to counteract drowsiness). Interestingly drowsiness was more frequently observed in dimenhydrinate when compared to placebo exposure (intra-individual cross-over design), thus motion-sickness induced drowsiness seems to be less severe than dimenhydrinate-mediated drowsiness. The authors conclude that dimenhydrinate works by depressing central nervous system activity and possibly by suppressing abnormal gastric myoelectric activity. Recent data indicate that dimenhydrinate may have a favourable role in antagonizing loss of body heat in seasick subjects [40]. Patients are prone to vomiting in established motion sickness grade MIIa (Table 10.13.1a) and beyond, thus parenteral adminstration via suppositories or i.v. fluid is more appropriate under these circumsta nces. This is reflected for instance by the ship medicine chest standard inventory defined by the German Federal Naval Authorities [[57]], which lists dimenhydrinate in the form of tablets, suppositories and i.v. vials.
• Meclizine (tablets, suppositories), another antihistamine, is considered to cause less drowsiness (marketed e.g. as Postafen™, Bonamine™, Dramamine II™). A controlled study in healthy volunteers in a ship motion simulator concluded that meclizine was superior in preventing motion sickness when compared to placebo, however being less potent than transdermal scopolamine [[58]]. Meclizine is widely used on ships carrying US passengers. It shows a comparatively favorable risk-benefit profile and thus meclizine may be considered a first choice antihistamine in motion sickness, which may also be administered to pregnant women and children beyond age of 12 years.
• Cinnarizine (tablets) is chemically related to first generation antihistamines and thus it also shares typical side effects such as drowsiness. Its utility is limited by relevant contraindications including history of myocardial infarction, asthma, depression, prostate gland hyperplasia, glaucoma, epilepsy, bradycardia, hypokalemia, use of aminoglycoside antibiotics, long QT-syndrome, alcohol abuse and Parkinson´s disease. Furthermore it must not be used during pregnancy or lactation. I should not be given to children below age of 18 unless individual risk-benefit assessment would turn out positive, which is unlikely given other alternatives. As with other antihistamines, combination or subsequent administration of anticholinergic drugs (scopolamine) is contraindicated. Still cinnarizine is commonly used on UK-based cruise ships, whereas it is not available in the U.S. or Canada.
• Promethazine (liquid; injectable for i.m. shots) also acts as an anti-H1 antihistamine and has formerly been used as an antipsychotic drug. Promethazine has sedative, anti-motion-sickness, anti-emetic, and anti-cholinergic effects. Meanwhile promethazine is also being used as a motion sickness remedy and is even available over the counter in some countries, whereas e.g. in the US and Germany it still requires prescription. Noteworthy there is controversial data on the dose response which does not seem to be linear: One study showed no clear increase in motion sickness tolerance vs. placebo by 50 mg promethazine in contrast to a 25 mg dose [[59]], whereas a former study [ [60] ] found the best relief from established (!) motion sickness by 50 mg promethazine given i.m.. Another relevant finding was that the 50 mg dose strongly impaired mental performance to a degree similar to 0.137 % blood alcohol. Given in effective doses promethazine seems to have a swift onset of action even in established motion sickness [[61]]. As with cinnarizine a range of caveats should be carefully regarded as detailed in the package leaflet, including co-morbidities such as leucopenia, prostate hyperplasia, hypertension, dementia, and glaucoma. Given this profile usage of promethazine may be considered in patients with advanced motion sickness, who are not expected to perform complex tasks thereafter. Promethazine i.m. is commonly administered in particular on cruise ships carrying U.S.-passengers. In general promethazine should be reserved for established motion sickness, a utility for prophylaxis is not supported by its risk-benefit ratio. Special caution should be given to an appropriate administration of the drug which should be strictly intramuscular or intravenous (slow infusion only), otherwise pain and tissue damage may result.
• So called second generation antihistamines with less central activity such as cetirizine or fexofenadine seem to be insufficient to prevent or treat motion sickness [[62]].
• The dopamine antagonist metoclopramide has both central (anti-dopamine-2 and anti-serotonin 5-HT3) as well as peripheral (serotonin 5-HT4-agonistic) properties. The former is deemed to reduce nausea and the latter to promote coordinated gastric propulsion, both quite desirable effects in imminent or established motion sickness. Thus MCP reduces intragastric pressure and normalises gastrointestinal motility. In contrast to treatment of established nausea, metoclopramide does not seem to work well in prophylaxis of motion sickness [[63]]. Furthermore oral metoclopramide may not always be efficacious in a treatment setting either. However, a combination with other motion sickness remedies like scopolamine or dimenhydrinate may improve response rates. Another option to maximise onset of action and efficacy is intravenous administration, as commonly practised in on cruise ships with Scandinavian medical staff.
• Ginger root and ginger preparations (Tablets, e.g. Zintona™) show (in particular prophylactic) potency against nausea and vomiting, confirmed in controlled clinical trials [[64]]. Grøntved et al. conducted a study on ginger root in naval cadets showing that the tendency to vomiting and cold sweating could be significantly reduced after ingestion of blinded ginger medication compared to placebo [[65]]. Lien et al. have shown that ginger ingestion (1000 mg) provided significant protection against gastric dysrhythmias as well as vasopressin elevations in volunteers [36]. Though the majority of studies has confirmed the efficacy of ginger and ginger preparations, an experimental study by Wood et al. [53] failed to demonstrate a significant effect. Meanwhile the pharmacological properties of ginger ingredients (gingerols and shogaols) have been further elucidated, detecting effects on the 5-HT3-receptor ion-channel complex, potential activity on substance-P receptors and on muscarinic receptors [[66]]. Other investigators have identified gingerol-binding TRPM8- type nociceptors in the middle ear.

A range of preparations is being promoted for use as prophylaxis against motion sickness, however some remedies are still lacking scientific proof of efficacy, including for example:

• Homeopathic preparations containing low quantities of vermouth (artemisia absinthum) such as Nausyn^Ò (tablets). This preparation also contains very low quantities of Ipecacuanha (D4) and Cocculus (D4), which both are pro-emetic in allopathic doses. A placebo-controlled rotation chair study by Huber [[67]] could not find a significant anti-emetic effect of Nausyn^Ò (tablets) when compared to placebo or dimenhydrinate.
• Vitamin C intake (e.g. via chewing ascorbinic acid tablets) has been promoted in order to reduce systemic histamine levels, however no conclusive scientific or clinical evidence to support this rationale has been provided yet.

Further investigational drugs against motion sickness comprise 5-HT-1A-serotonin-agonists, neurokinin-type1-receptor-antagonists [[68]], and specific vasopressin-antagonists, however clinical data are still scarce for most. Further research may also warranted with regards to:

• Ondansetron: Despite already being listed in the international medical guide for ships for “preventing vomiting and sea-sickness” the anti-emetic drug, a 5HT3-receptor-antagonist primarily used in chemotherapy-induced nausea, has recently been in investigated in a clinical motion sickness study, showing no significant effect [42].
• Modafinil: This stimulant (increasing norepinephrine, dopamine and histamine levels in the CNS) is approved for treatment of narcolepsy in the EU. Modafinil has been investigated in a controlled study vs. placebo and a combination with oral scopolamine and failed to show protective effects against motion sickness [[69]].
• Baclofen: This drug is known for its muscle-relaxing, anti-spastic, and anxiolytic properties, and data indicate potential utility in motion sickness [[70]].

Interactions between motion sickness remedies: Given similarities of potential undesirable drug effects, in particular drowsiness and anticholinergic effects, scopolamine and dimenhydrinate (or meclizine, promethazine, or any other antihistamine) should NOT be co-administered, or be given subsequently, unless sufficient time for washout is warranted, e.g. 10-12 hours after ingestion of a dimenhydrinate tablet. In younger patients (< 45 yrs) with known high susceptibility to develop severe motion-sickness, scopolamine would be the drug of first choice, since starting with dimenhydrinate would preclude latter use of the more potent alternative. Generally these issues are more relevant in middle-aged and elderly patients and special caution should be taken with regard to the contraindications and caveats listed in table 3.

Pharmacotherapy (prophylaxis and treatment) of seasickness in specific patient groups:

• Phamacotherapy of motion sick children may prove difficult since many caveats and restrictions have to be regarded concerning the most widely used medications (in particular antihistamines, scopolamine, cinnarizine, and metoclopramide; table 10.13.3). Thus precautionary measures (see 10.13.5 Prophylaxis) become even more important here, including ginger preparations (age of 3-5 years: freshly brewed tea from 1g of ginger, add sugar or honey; from age of 6 years onwards: preferably ginger tablets) and acupressure bands. Scopolamine patches may be given from the age of 10 years onwards, meclizine and dimendydrinate are labelled for use from the age of 12 years. Children in particular should not play games or watch videos on tiny screens (e.g. Nintendo, iPod Touch etc.), conversely listening to their favorite music with eyes closed can be very helpful. Severly motion sick children need special attention and care, including sufficient rehydration and effective protection against risk of falling (over board) or other injury.
• Likewise pharmacotherapy of women during pregnancy and lactation requires special caution (e.g. regarding contraindications for use of cinnarizine and to some extend als promethazine). Given their current FDA B-ratings (no proven risk in humans), meclizine and dimenhydrinate may be considered appropriate, if ginger and non-pharmacological approaches have failed. In pregnancy scopolamine should be reserved for very severe refractory motion sickness only, e.g. when more appropriate medication has failed and fluid loss needs to be stopped. Overall meclizine may be regarded the treatment of choice during pregancy [[71]].
• Elderly passengers often represent the majority on cruise ships and when getting motion sick, these patients may also pose a challenge in chosing the appropriate medication. Given the vast number of caveats with promethazine and cinnarizine these drugs should be avoided. Scopolamine too should be used with caution only, in particular regarding common co-morbidities sich as urinary retention, diabetes, arrhythmia, hepatic impairment or glaucoma. A more favorable overall risk-benefit ratio in this age-group may be offered by meclizine and/or metoclopramide.
• Though ship crew members will most often be well adapted to motion stimuli, treatment for seasickness may become necessary. Medical staff should inquire how specific anti-seasickness medication has worked and been tolerated by the crew member on past incidences and if and how the individual performance was affected. The choice of pharmacotherapy should account for the specific tasks of the crew member: In case of dangerous workplaces like engine rooms or deck areas, drugs associated with a high rate of drowsiness or dizzyness (e.g. certain antihistamines) ought to be avoided. Similarly in pharmacotherapy of crew with mental tasks to perform and a high level of responsibility (e.g. navigation officers, watch officers, VHF operators) such drugs should be avoided. Ginger, metoclopramide or scopolamine would be preferred options. Meclizine is considered to cause less drowsiness than other antihistamines and thus should be a feasible option as well. Add-on treatment with ephedrine may be considered in crew with tasks requiring high mental performance [[72]].

Severely motion sick patients having vomited repeatedly need special care and attendance:

• Most importantly the patient must be removed from areas of the ship with risk of falling overboard (e.g. deck areas) or places with increased risk of injury (e.g. engine room).
• The motion sick person should be taken off duty and be replaced by a deputy (back up)
• Vomit should be wiped away immediately, and dry clean clothes be put on
• The patient should be offered sips of water to rinse the mouth, thereafter fresh (non-sparkling) water to drink
• Repeatedly offer special drink for rehydration (oral electrolyte solution, table 10.13. 4)
• In case of sustained vomiting with signficant fluid loss and apathy consider infusion of sterile 0.9 % NaCl solution.
• Appropriate medication should be considered
• The patient should be offered to lay down and rest in a bunk, eyes closed
• A designated person should be looking after the seasick patient if number of crew allows for
• Offer a Music-Player (MP3, iPod, CD-Player) with favorite music
• Keep telling the patient reassuringly that symptoms will improve

Table 10.13. 4: Oral Rehydration Solution (ORS)*

*Alternatively, use prefab rehydration solution powder (e.g. Elotrans^Ò) and dissolve in water

** The WHO 2006 ORS recipe would also contain trisodium citrate for compensation of diarrhea mediated acidosis. Since not acidosis but alcalosis is the issue in motion sickness due to loss of acids via vomit this additive is not required here.

10.13.7 Summary

• Seasickness may vary in symptoms and severity, ranging from mild epigastric discomfort to severe forms with repeated vomiting, subsequent dehydration and apathy.
• When recruiting personnel for ships, the MMSQ-short questionnaire may serve to identify incumbents with increased sensitivity for seasickness.
• Though seasick patients usually recover well, seasickness should be regarded a treacherous condition, potentially impairing mental and physical performance of passengers and seafarers alike.
• A seasick crew may have deleterious impact on safety (all aspects of safely handling the ship, including navigation).
• Motion-sickness-mediated mental impairment may actually be more grave than predominantly mild side effects of anti-motion-sickness drug, however this may vary depending on the drug and the individual. This is relevant in particular for seafarers with operational tasks.
• Vomiting and altered drug absorption may put patients at risk of insufficient medication, therefore patients with chronic diseases in particular should be monitored carefully for symptoms or signs of exacerbation (e.g. diabetes, epilepsy) .
• Pharmacological and behavioural prophylactic measures may help to avoid or attenuate seasickness symptoms in many cases.
• When seasickness symptoms occur, appropriate treatment should be started early on. In case of nausea (malaise IIa + III) avoid oral medication and administer drugs either via rectal, i.m., i.v., or transdermal route.
• Always check for any prior medication (including medication for chronic diseases) and avoid subsequent or parallel co-administration of anti-histamines and scopolamine.
• Carefully mind restrictions of some anti-motion-sickness remedies with regards to children or pregnant women.
• In the elderly carefully inquire about co-morbidities and contraindications to common motion sickness remedies, e.g. glaucoma, urinary retention or arrhythmia.
• In emergency situations requiring abandoning ship, fluid loss and either cold or heat (depending on circumstances, sea area, weather and integrity of the rescue vessel) may pose serious threats. Both body temperature loss as well as fluid loss are aggravated by seasickness, thus prophylactic medication should become part of rescue algorithms. All passengers and crew should receive motion sickness medication (scopolamine patch, dimenhydrinate supp. or meclizine supp.) in due time before embarkation on a life raft or survival craft.

References

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