Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter.
Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.
OCR for page 79
79
APPENDIX B
U.S. Military Policies Regarding Use of Hypnotics and Stimulants
INTRODUCTION length of the sleep period, and the probability of an earlier-
then-expected awakening, which may increase the risk of sleep
In January 2009, a team of six prominent members of the inertia effects. Table B1 lists the categories of hypnotics and
Aerospace Medical Association (AsMA) published a position their conditions of use as outlined by Caldwell et al. (2009).
paper regarding the use of fatigue countermeasures in aviation. Each of the U.S. military services has its own policy con-
The position paper (Caldwell et al. 2009) espouses numerous cerning the use of hypnotics. Table B2 summarizes the U.S.
operator fatigue mitigation strategies and countermeasures military policies for hypnotic use (predominately specified
highlighting the need for sleep management, work-rest sched- for military aviation operations). Just as is followed with the
uling, copious use of nap-taking, and so on. Because of the military use of stimulants, a ground test with hypnotics under
implications of that position paper for all transportation modes, controlled conditions is necessary prior to use during opera-
it is of particular importance in this synthesis to reference their tions. The U.S. Navy guidance explicitly forbids administration
comprehensive coverage of research and recommendations
of more than one dose of a hypnotic per 24-h period, with no
concerning the use of pharmacological agents (both hypnotics
more than two doses of consecutive use of temazepam. There
and stimulants) as countermeasures to sleep-deprivation,
is also guidance for planning and briefing in the grounding
fatigue, and associated problems in aviation operations (both
restriction (U.S. Navy OPNAV Instruction 3710.7S 2001).
military and civilian aviation situations are addressed). Their
As with other medications, the use of hypnotics is voluntary.
work also has implications for the commercial driving com-
The reader is referred to the review of military pharmacological
munity (truck and bus/motorcoach operators). The treatise
policies by Caldwell et al. (2009) for details on the specific
here is largely extracted from that position paper (Caldwell
et al. 2009). "treatment protocols" for use of temazepam, zolpidem, and
zaleplon in military aviation settings.
Although differences exist between civil and military operations,
it is clear similar factors and conditions lead to fatigue in both Caldwell et al. (2009) also look toward the potential
civilian and military aviation environments and fatigue mitiga- military aviation application of some of the newer hypnotics
tion strategies for both contexts should be scientifically based.
available to help with sleep maintenance because they
Understandably however, different regulations and operational
considerations have resulted in fatigue countermeasure approaches offer a shorter half-life than the extended longer half-life
that differ in important ways. For example, a variety of pharmaco- of temazepam. For example, the extended-release zolpidem
logical countermeasures have been approved for use in certain (Ambien-CR®) improves sleep maintenance beyond that of
circumstances by U.S. military aviators but not by civilian aviators.
The current prohibition regarding use of pharmacological counter-
zolpidem (Greenblatt et al. 2005). Eszopiclone (Lunesta®)
measures by civilian pilots can be attributed to safety concerns has a half-life of 5 to 6 h with minimal residual drug effects
and issues of adequate policies for oversight. The military ser- after as little as 10 h post-dose (Leese et al. 2002). Ramelteon
vices have addressed these issues through targeted research, (Rozerem®) is a novel hypnotic in that it targets the melatonin
explicit policies on medical oversight, and recognition of the
sometimes overriding importance of operational considerations receptors in the brain in order to regulate the body's sleepwake
(e.g., US NAVMED P-6410 2000). cycle, and research indicates this drug is efficacious for
sleep onset, but not for sleep maintenance (Lieberman 2007).
The use of pharmacological countermeasures to fatigue in civilian Caldwell et al. also mention the new hypnotic indiplon, which
(but not military) pilots is addressed by Caldwell et al. (2009). should be on the market in the near future. Indiplon is similar
in structure to zaleplon and has a half-life of approximately
HYPNOTICS AND AVIATION 1.5 h and is being formulated with a modified release that
will extend its half-life to aid in sleep maintenance (Ebert
For circumstances where sleep is difficult to obtain in et al. 2006). There also are new compounds that are rapidly
operational contexts, pharmaceutical strategies (espoused by absorbed and that have a short half-life, and several have
Caldwell et al. 2009) include U.S. Air Force and U.S. Army the ability to increase both slow-wave sleep and slow-wave
approval of limited use of temazepam, zolpidem, and zaleplon. activity, which improves sleep efficiency. These compounds
[Only the U.S. Army continues to authorize limited use of may improve sleep efficiency to the point that effective wake-
triazolam (Halcion®) for pre-deployment rest or sustained fulness can be sustained on fewer than the 8 h of daily sleep
operations--although in actuality it is rarely prescribed]. These now required (Caldwell et al. 2009). These developments
three hypnotics Caldwell et al. (2009) state can optimize the should be carefully watched to determine their potential
quality of crew rest in circumstances where sleep is possible, applicability to the commercial driving community.
but difficult to obtain. The choice of which compound is
best for each circumstance they say must take several factors As for current civilian aviation policy, the FAA only allows
into account, including time of day, half-life of the compound, limited use of zolpidem (Ambien®) and at that no more
OCR for page 80
80
TABLE B1
LIST OF HYPNOTICS AND THEIR USES
Generic Average
Name Brand Name Dosage Half-Life Recommended Use Cautions
Temazepam Restoril® 1530 mg 9h Sleep maintenance; Need 8 h sleep
Euhypnos® daytime sleep period; not
Normison® recommended if
Remestox® on-call
®
Norkotral
Zolpidem Ambien® 510 mg 2.5 h Sleep initiation;
®
Stilnox intermediate-length naps;
Myslee® assisting early sleep onset
due to early bedtimes from
shift or time zone change
®
Zaleplon Sonata 510 mg 1h Sleep initiation; short naps; Not recommended
Starnoc® assisting early sleep onset if on-call
due to early bedtimes from
shift or time zone change
Source: Aviation, Space and Environmental Medicine (Caldwell et al. 2009).
than twice per week, stating it cannot be used for circadian with varying length of action that policy would encourage
adjustment. In addition, there is a 24-h grounding policy for selection of the appropriate drug for the specific time of use.
any pilot who uses zolpidem. Caldwell et al. (2009) suggest These authors offer recommendations for permitting use of
that the FAA's policy that hypnotics not be used for circadian additional hypnotics in civilian aviation. Interested readers
disruption is overly restrictive because it is precisely for this are referred to Caldwell et al. 2009 for details.
reason that hypnotics would be useful for pilots crossing
multiple time zones or flying early morning flights. They Caldwell et al. (2009) suggest that sleep-promoting
suggest that rather than permitting a choice of only one compounds can be useful in operational contexts where there
hypnotic, if they allowed a choice of a variety of hypnotics are problems with sleep initiation or sleep maintenance.
TABLE B2
U.S. MILITARY POLICIES FOR USE OF HYPNOTICS
Medication Dose Half-Life Grounding
U.S. Army Rest Agent Policy
Temazepam (Restoril®) 15 or 30 mg 8.012.0 h 24 h
®
Triazolam (Halcion ) 0.125 or 0.25 mg 2.04.0 h 9h
Zolpidem (Ambien®) 5 or 10 mg 2.02.5 h 8h
Zaleplon (Sonata®) 5 or 10 mg 1.0 h 8h
U.S. Air Force No-Go Pill Policy
Temazepam (Restoril®) 15 or 30 mg 8.012.0 h 12 h
Triazolam (Halcion®) Not authorized N/A N/A
®
Zolpidem (Ambien ) 10 mg 2.02.5 h 6h
Zaleplon (Sonata®) 10 mg 1.0 h 4h
U.S. Navy Sleep Initiator Policy
Temazepam (Restoril®) 15 mg 8.012.0 h 7h
Triazolam (Halcion®) Not authorized N/A N/A
Zolpidem (Ambien®) 5 or 10 mg 2.02.5 h 6h
Zaleplon (Sonata®) Not authorized N/A N/A
Source: Aviation, Space and Environmental Medicine (Caldwell et al. 2009).
N/A = not available.
OCR for page 81
81
However, they state that as with all medications there are that in sustained aviation operations the occasional use of the
both benefits and risks associated with the use of hypnotic alertness-enhancing medications such as dextroamphetamine
compounds. The risks should be considered by the prescribing (authorized by all three U.S. military services) and modafinil
physician (flight surgeon) and the individual pilot before (authorized for use in the U.S. Air Force) can often signifi-
the decision to use hypnotic therapy is finalized. If the crew- cantly enhance the safety and effectiveness of sleep-deprived
member is likely to be called back to duty earlier than antici- personnel.
pated, then a hypnotic of any type probably should not be used
because this would put the pilot at risk of performing flight
duties before the medication has been fully metabolized. Modafinil (ProVigil®)
Particular research studies on modafinil were described in this
Although temazepam, zolpidem, and zaleplon are widely
synthesis in chapter four. Caldwell et al. (2009) suggested
recognized as being both safe and effective, operational
that modafinil is gaining popularity as a way to enhance the
personnel should be cautioned about potential side effects
alertness of sleepy personnel, largely because it is considered
and instructed to bring these to the attention of their physician
safer and less addictive than compounds such as the amphet-
should they occur (Caldwell et al. 2009). For reasons related
to anticipated side effects, military personnel are required to amines. Modafinil also produces less cardiovascular stimulation
receive a test dose of the hypnotic of interest under medical than amphetamine and, despite its half-life of approximately
supervision before using the medication during actual oper- 12 to 15 h (Robertson and Hillriegel 2003), the drug's impact on
ational situations. Further, even after the test dose yields sleep architecture is minimal. Caldwell et al. (2009) reminded
favorable results and it is clear that operationally important side readers that modafinil has not been as thoroughly tested as
effects are absent, hypnotics should be used with particular dextroamphetamine in real-world operational environments
caution when the aim is to aid in advancing or delaying cir- and some data suggest modafinil is less effective than amphet-
cadian rhythms in response to time zone shifts. Reviews by amine (Mitler and Aldrich 2000). Caldwell et al. (2009)
Nicholson (1990), Stone and Turner (1997), and Waterhouse indicated that the U.S. Air Force has approved the use of
et al. (1997) offer detailed information on this rather complex modafinil in certain long-range combat aviation missions, and
issue (Caldwell et al. 2009). it is likely the U.S. Army and the U.S. Navy soon will approve
of use of modafinil as well.
STIMULANTS DURING MILITARY OPERATIONS
Amphetamine (Dexedrine®, Dextrostat®)
There is a sizeable literature base describing U.S. military
research, mostly by medical research laboratories, on the Dextroamphetamine (5 to 10 mg) has been authorized for use
application of a select number of stimulant drugs by military by all three U.S. military services for certain types of lengthy
personnel, to demonstrate possible protocols for usage dur- flight missions (i.e., 12 or more hours of flight). Some of the
ing training or actual military operations. In particular, work research described in chapter four supported policy decisions
with aviators has examined dextroamphetamine stimulants concerning use of amphetamines in the three U.S. military
(e.g., predominately dexedrine) with helicopter pilots (e.g., services (for details, see Caldwell et al. 2009). Caldwell et al.
Caldwell et al. 1995, 1997, 2000a, b; Caldwell and Caldwell (2009) recommend the use of dextroamphetamine in doses of
1997, 2000a, b), with fighter jet pilots (e.g., in simulators by 10 to 20 mg (not to exceed 60 mg per day) for situations in
Caldwell et al. 2004), and in actual combat operations reported which heavily fatigued military pilots simply must complete
by Schultz and Miller (2004a, b) and Gore et al. (2010), in the mission despite dangerous levels of sleep deprivation. The
bomber aircraft operations (Kenagy et al. 2004); and exem- following stimulant use protocol guidance, which Caldwell
plified in the United Kingdom's Royal Air Force use of pemo- et al. (2009) attributed to the U.S. Air Force, is extracted from
line in air operations (e.g., Nicholson and Turner 1998). It is their report.
beyond the scope of this synthesis to detail the numerous
studies and their findings here. U.S. Air Force Combat Aviation Operations Guidance
for Use of Stimulants
The same team of AsMA scientists mentioned earlier · Prior to the operational use of dextroamphetamine
regarding hypnotics also detailed research that informed U.S. or modafinil, an informed consent agreement must
military policies regarding the use of stimulants in military be obtained to ensure that crews are fully aware of
both the positive and the potential negative effects
aviation (Caldwell et al. 2009). These authors stated that of these compounds.
one option for sustaining wakefulness of flight crews during · The decision to authorize the use of alertness-
extended missions wherein adequate crew rest is not feasible enhancing compounds should be made by the Wing
is to employ alertness-enhancing medications (stimulants). Commander in conjunction with the Senior Flight
Caldwell et al. (2009) prefaced their treatise by stating that Surgeon.
· All distribution of alertness-enhancing medications
these compounds should not be considered a replacement for must be closely monitored and documented.
adequate crew rest planning and they should never be con- · Ground testing (during non-flight periods) is required
sidered a substitute for restorative sleep. However, they state prior to operational use.
OCR for page 82
82
· The currently authorized dose of dextroamphetamine authorized for use in any type of civil aviation operation.
is 5 to 10 mg, and although the dosing interval is not Caldwell et al. (2009) suggested that because civil aviation
explicitly stated, a 4-hour interval is often recom- operations generally are more predictable than military oper-
mended. No more than 60 mg should be administered
in any 24-hr period, and often, no more than 30 mg ations, and since prolonged periods of sleep deprivation are
are administered. not the norm in civil operations (but are almost unavoidable in
· The currently authorized dose of modafinil is 200 mg the military), meaning in civil aviation that other allowances
every 8 hours, not to exceed 400 mg in any 24-hour can be planned on, it would seem prudent to withhold wide-
period; however, recent F-117 research has indicated spread authorization of prescription alertness enhancers in
that 100 mg doses also are efficacious (and this lower
dose is authorized as well). the civilian aviation sector.
· The use of alertness-enhancing compounds normally
can be authorized in fighter missions longer than Intense military operations are generally time limited, in
8 hours or bomber missions longer than 12 hours that they expose military pilots to only relatively brief periods
(although exceptions can be made). in which intense sleep deprivation necessitates administration
· Caffeine generally is not considered to be a suitable
alternative for modafinil or dextroamphetamine; how- of appropriate counter-fatigue medications (Caldwell et al.
ever, caffeine in the form of foods or beverages may 2009). Because the continuous combat conditions in Iraq
be consumed without restriction. Caffeine in the form and Afghanistan have now been extended over several years,
of tablets or capsules can only be used after flight many military pilots have been exposed to pharmaceutical
surgeon approval. intervention on what comes closer to chronic rather than
Source: Aviation, Space and Environmental Medicine acute circumstances. A concern in civil aviation operations
(Caldwell et al. 2009). has always been that if such medications were authorized,
commercial pilots might continue day-in and day-out for weeks,
U.S. Army and U.S. Navy guidance is mostly consistent months, years, and even for the duration of a pilot's career,
with that of the U.S. Air Force (listed earlier), with the most which in effect could potentially expose moderately fatigued
notable exception being that modafinil is not currently autho- pilots to years of chronic medication use. Caldwell et al. (2009)
rized in the Army or Navy. The U.S. Army guidance for use take the position that this difference between military and civil
of dextroamphetamine endorses the administration of 5- or aviation operations argues against widespread authorization
10-mg doses and specifies that no more than 30 mg may be
of alertness-enhancing drugs in civil operations.
used in any 24-h period. The medication is not be used to
sustain wakefulness for longer than 64 continuous hours.
U.S. Navy guidance suggests dextroamphetamine be admin- ASSESSMENT OF MILITARY USE OF HYPNOTICS
istered in 5-mg doses, which may be repeated every 2 to 3 h; AND STIMULANTS TO SUSTAIN ALERTNESS
however, total dosage should not exceed 30 mg in any 24-h
period. The Navy does not specify an upper level for the To the MaineWay synthesis team it would appear that the
duration of any period of continuous wakefulness, but it is cautions mentioned previously for treating differences in
clear that extended periods without sleep should be avoided military versus commercial and civil aviation operations hold
(Caldwell et al. 2009). After citing many research reports equally true, if not more so, for the commercial driving and
related to the topic, Caldwell et al. recommended that all transport industries. Much of what takes place in operational
three services sanction the use of modafinil under guidance employment of chemical countermeasures in select military
consistent with that currently followed by the U.S. Air Force applications does not readily transfer one-for-one to potential
(and described earlier). utilization of pharmaceutical countermeasures in commercial
driving settings. This is particularly true when one considers
Caffeine use is a relatively uncontrolled stimulant in the that the military's policies include ensuring tight controls over
three U.S. military services, and Caldwell et al. (2009) recom- the use of psychoactive substances in training and during
mended that aircrews should avoid habituation to caffeine military operations. This just would not be feasible or prac-
and take advantage of its cortical stimulant properties when tical in commercial driving scenarios.
it is needed to help ensure safe operations. More specifically,
when aircrews are not suffering from the effects of fatigue, However, there are elements of the military medical research
they should limit their total daily caffeine consumption from all findings that can benefit the commercial driving community,
sources to 200 to 250 mg of caffeine per day. Additional doses such as the possibility of use of stimulating compounds such
of caffeine should be used during situations in which fatigue as modafinil and caffeinated chewing gum. Under current
elevates the risk of a mishap. In any 24-h period the total hours of service rules, which require daily ten-hour off-duty
amount of caffeine consumed should not exceed 1000 mg. rest periods and include such facets as 34-h weekly restart rest
Aircrew members are to be reminded of the 4 to 6 h half-life periods, the military protocols used with ultra-short hypnotics
of circulating caffeine and preplan its use such that post-duty to induce sleep might make some sense in selected applica-
day sleep is not disturbed by the caffeine consumed. tions in the commercial driving industries. Continuing new
developments in military medical research and applications
With the exception of caffeine and various nutritional sup- should be carefully monitored for their potential applications
plements, no alertness-enhancing medications are currently for safe transportation operations.
