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excerpts
from
Performance
Maintenance During Continuous Flight Operations
A Guide for Flight Surgeons
(NAVMED P-6410)
Naval Strike and and Air Warfare Center
1 Jan 2000
Anti-Fatigue
Medications
WHILE NOT A SUBSTITUTE FOR WISE MANAGEMENT THERE ARE TIMES TO CONSIDER
THIS TYPE OF INTERVENTION
Performance Maintenance
Vice Enhancement
An unpleasant image frequently comes to mind when the
topic of anti-fatigue medications and aviators is raised.
This is of an exhausted pilot who is too tired to fly but is
given a high dose of stimulant and repeatedly launched
into combat with the expectation that he will perform
better than ever before. From this scenario it changes to
the aviator suffering from insomnia and other side effects
from the stimulant who now requires repeated doses of a
sedative to overcome the stimulant medication effects.
This unfortunate
scenario represents the extreme of an
attempt at “performance enhancement.” While limited
enhancement may be achievable in the future the
appropriate use of anti-fatigue medications today is in the
role of “performance maintenance.” Aviators already
fly extremely well; the challenge is to identify when
fatigue causes periods of degraded performance and then
intervene only to maintain an existing level of capability.
This intervention would take the form of helping the
aviator sleep (thus preventing fatigue) or keeping him
awake and alert during the low task phase of a mission.
Non-Pharmacologic
Strategies
The use of non-pharmacologic strategies prior to using
any medication is essential. This includes deferral of
routine non-flying duties, flexible scheduling, and use of
frequent naps. “Strategies and Ideas” on page 12 contains
specific suggestions for the airwing, squadron, individual
aviator and flight surgeon.
History
The use of medications to maintain performance in
aviators is not a new idea. During the Falklands conflict
sedatives were used by the British to regulate sleep for
pilots (13,14). Amphetamines were used by the British
(15) and Germans (16) in WWII . During Vietnam both
the Air Force and Navy made amphetamines available to
aviators. Intermittently since Vietnam up through Desert
Storm the Air Force has used both amphetamines and
sedatives in selected aircraft for specific missions (17).
While not used for performance maintenance, dextroamphetamine
(Dexedrine) was administered frequently in
combination with scopalomine to combat motion sickness
during primary Navy flight training. A similar
combination of meds is currently utilized by NASA to
combat space motion sickness during shuttle flights.
Stimulants To
Maintain Alertness
Amphetamines have both central and peripheral actions.
In the CNS they are a powerful sympathomimetic amine
and serve to increase alertness, focus attention, elevate
mood, decrease appetite, and improve concentration.
Peripherally, both systolic and diastolic blood pressure
will be raised with a reflex decrease in heart rate.
Dextroamphetamine (Dexedrine) shows strong central and
peripheral effects while methamphetamine has less
peripheral action.
At low dosages amphetamines
primarily increase alertness
with significant side effects only beginning as the doses
are increased. Well rested subjects evaluated in the
laboratory showed that 5 mg of dextro-amphetamine
(Dexedrine) counteracted small performance decrements
caused by scopolamine (18). An intermittent low dose
regimen, therefore, has the capability of maintaining
aviator performance yet avoiding undesired medication
effects. This is consistent with reports from USAF
pilots during Desert Storm who stated that 5 mgs of
dextro-amphetamine (Dexedrine) helped maintain
alertness without causing other changes in mood or
perception (19).
Caffeine is
also effective at reversing some of the effects
of fatigue. It compares favorably to amphetamine in
improving cognitive performance but is less effective in
maintaining alertness (20). Based purely on efficacy, it is
a second choice to amphetamine. Due to its low abuse
potential and wide availability, however, caffeine still
offers significant utility (especially in ground personnel).
Caffeine was used successfully during flights over Iraq
supporting Operation Southern Watch in August 1992 (21).
Sleep Initiators
Benzodiazepines produce the “most natural” quality of
sleep and are therefore good candidates for sleep
initiators. Two significant medication effects are seen:
drowsiness (the desired hypnotic action) and amnesia of
events during the time the medication has an effect
(called anterograde amnesia).
The most significant
drawback to benzodiazepines is
anterograde amnesia. For the military aviator this raises
the possibility of taking the medication, going to a brief,
taking-off and then not remembering what he was told
to do. A period of restriction from flight planning,
briefing or flying is therefore mandatory following use
of benzodiazepines. The restriction for Temazepam
(Restoril) is seven hours and is derived from two
primary sources. A single laboratory study of a 15 mg
dose of temazepam found neither hangover nor amnesia
seven hours later (22). Additionally, experience in
Desert Storm did not reveal adverse reports from
aircrew who flew six to eight hours after using
Temazepam (Restoril) (19). A 30 mg dose does not
necessarily produce better sleep and has a higher
incidence of hangover effect and amnesia (22).
Unfortunately, the
demands of strike planning and other
non-flying duties may preclude a seven-hour restriction
from duty. Another benzodiazepine that has a shorter
elimination half-life is Ambien (zolpidem). Mean peak
concentrations occur at 1.6 hours after absorption and
the mean elimination half-life was around 2.6 hours.
The USAF cleared operational forces to use Ambien in
1996. For faster sleep onset it is recommended that
Ambien be taken on an empty stomach.
Repetitive Dosing
The risk of drug accumulation from repetitive dosing
warrants serious consideration. One pharmacologic rule
of thumb suggests that to avoid accumulation dosages
need to be repeated at an interval no less than four times
the half-live. The maximum acceptable half-life for a
medication used daily for extended periods, therefore, is
about six hours. The half-lives of the active components
or metabolites for dextro-amphetamine (Dexedrine) is
about ten hours, Restoril ten hours and Ambien ten hours.
Variability in the
half life and metabolism of
benzodiazepines and amphetamines is related to the
volume of distribution, body fat, drug lipophilicity, and
drug elimination. Half life of benzodiazepines is lower
in young men because of larger body volume, lower
body fat, and active drug elimination. There may be
variations in half-life in the population of military
aviators due to gender and age. A ground “pretest” of
these medications will help each aviator understand their
individual effects from the medications and when they
specifically notice the onset of effects.
Stimulant Side
Effects And Adverse Reactions
Undesired side effects from amphetamine use
potentially include increased sleep latency, anorexia,
euphoria, hypertension, idiosyncratic reactions, cyclic
use of a stimulant/sedative combination to maintain
performance or outright abuse (24). These symptoms are
primarily dose related and are not expected with 5-10
mgs of dextro-amphetamine (Dexedrine). Insomnia is
possible if aircrew use the medication within two hours
of sleeping but this can be avoided with appropriate
education and training. Idiosyncratic reactions are rare,
and should be detected during pretesting. Finally, abuse
is possible but felt to be unlikely given the professional
nature of aviators, the limited and well defined
circumstances within which these medications will be
used, and by close aeromedical supervision.
No formal records
are available from the use of the
scopolamine-Dexedrine combination for motion
sickness by the Navy training command. Many years of
use, however, did not generate reports of adverse
reactions or abuse.
Medication Interactions
Interactions with Chemical Warfare (CW) treatment
medications (pyridostigmine, atropine and 2-PAM
Chloride) and amphetamines or benzodiazepines are not
described by the Drug Therapy Screening System
(MICROMEDEX). Caffeine may aggravate arrythmias
particularly if used with amphetamines.
Benzodiazepines will interact with other CNS
depressants, such as alcohol, opiates and antihistamines
(diphenhydramine). Temazepam (Restoril) and Ambien
should not be taken together.
Importance of
Self-Regulation
The delegation of responsibility for use of these
medications to the individual aviator, with close followup
by the flight surgeon is extremely important and the
key to success in the operational arena. This principle
was strongly emphasized by the Air Force during Desert
Storm. If the operational tempo is intense enough to
generate significant fatigue, then an overly restrictive
medication protocol will probably lose its utility due to
lack of flexibility. Aviators, by their nature, are efficient
at using tools given to them to achieve specific goals.
Anti-fatigue medications are no exception.
Although significant
responsibility is delegated to the
aviator the amount of medication issued at one time
should be limited to what is needed for one or two
flights. This allows the flight surgeon to remain closely
involved and limits the potential for misuse of the
medication either on a one time or recurring basis.
Aircrew Briefings
As the final decision to use stimulants or sedatives is
delegated to the aviator his understanding becomes key
to the success of the protocol. The need for a quality
briefing by the flight surgeon with regular follow-up for
advice cannot be overemphasized.
USAF Experience in Desert Storm
AN IN-DEPTH LOOK AT ONE SUCCESSFUL SQUADRON
Background
Stimulant medications dextro-amphetamine
([Dexedrine] 5 mg or recently caffeine 200 mg) were
first used in SAC in 1960 and TAC in 1962. While no
formal data gathering was done no problems with these
stimulants or sedatives are reported. Recently SAC did
not use stimulants but authorized Restoril in single/dual
seat aircraft. Following Desert Storm an anonymous
survey of deployed fighter pilots was completed. 464
surveys were returned (43%). For Desert Storm: 57%
used stimulants at some time (17% routinely, 58%
occasionally, 25% only once). Within individual
units, usage varied from 3% to 96%, with higher
usage in units tasked for sustained combat air
patrol (CAP) missions. Sixty one percent of
those who used stimulants reported them
essential to mission accomplishment (17).
F-15 Squadron’s
Experience (19)
This squadron deployed flying to Saudi Arabia
as part of Desert Shield with TRANSPAC
flights lasting up to 16 hours non-stop.
During Desert Storm they flew
approximately 7000 hours in 1200
sorties using a pool of 35 pilots and
shot down a total of 16 MiG
aircraft. It is notable that the
squadron had the fewest pilots
assigned yet flew more flight
hours and shot down more
aircraft than any other F-15
squadron in-theater.
Implementation
of
Anti-Fatigue Medications
Squadron pilots were briefed clearly and completely on
the characteristics, recommended dosing, and intended
use for both stimulant and sedative medication.
Medication, once issued, was considered to “belong to
the pilot.” The policy of the commanding officer was
that all pilots would always fly with stimulant
medication available, however, the decision to use it
was left to the individual. Sedative medication was
not allowed to be carried in the airplane to prevent its
accidental use in place of stimulant.
The stimulant, described
as the “go-pill”, was 5 mg
dextro-amphetamine (Dexedrine). The recommended
dose was one or two taken orally every four hours. As
there is a 45-60 minute delay in onset of effect for the
stimulant it was recommended that they use it when the
early symptoms of fatigue appeared. They were then
given four to six dextro-amphetamine (Dexedrine)
tablets which were replaced as needed. In practice most
aviators used a 5 mg dose, repeating it every two to
three hours. While some took the go-pill outbound on
missions with the thought that it would act as a
performance enhancer the majority used the medication
in the early morning hours or just after sunrise during
extended combat air patrol (CAP) missions. If there was
enemy activity staying alert was not a problem. For long
periods during the war, however, the missions involved
flying to a CAP station, circling, then returning to base
for seven hours of uneventful flight time.
The sedative was
15 or 30 mg of Temazepam (Restoril)
used as an aide for sleep and was called the “no-go”
pill. While a 12 hour period of grounding was
recommended pilots used this medication
and began flight planning within six
to eight hours without reporting
any adverse effects, including
amnesia or “hangover” effect.
The no-go pill was used less
frequently than the go pill.
While based on an extremely
limited and subjective sample,
it appeared that the younger
aviators favored the go-pills and
the older ones the no-go pills.
Medication use was
approved by the commanding
officer who was regularly kept apprised by the flight
surgeon. Medication was carried personally by the
flight surgeon as the pilots were too busy flying or
planning to routinely come to sickbay. Additional pills
were dispensed as needed with amounts recorded in a
small logbook. Frequent visits to the scheduling office
and his presence most of the time in the squadron office
allowed him to know the aviators’ schedules and keep
track of individual tasking.
Concerns and Adverse
Effects
A number of pilots used more medication than the
flight surgeon thought they needed at the time. When
the tasking went down, however, their behavior
changed and medication use stopped. He has not
worried about anyone since and now feels that there
was no abuse of either drug, just individual differences.
Insomnia following
amphetamine use was not
normally seen. Two pilots reported difficulty
sleeping when they used the medication within
an hour or so of landing. This
was due to poor planning or
in one case recall of the
mission. Pilots quickly
learned the characteristics of
the stimulant and used it
efficiently.
When Temazepam (Restoril)
was used for insomnia it was
usually as a result of
work/combat tasking. Cyclic
use of stimulants and sedatives
in combination was not seen. No
tolerance or need to increase the dose
of stimulant or sedative was reported nor
was there a post-stimulant “crash.” No
adverse or idiosyncratic reactions were noted.
While weight loss was common during the war it
was not felt to be due to amphetamine induced
anorexia. No one reported a reduction in G tolerance.
One pilot did report that amphetamine significantly
reduced or eliminated the onset of spatial disorientation
during aerial refueling at night in bad weather.
Squadron Flight
Surgeon Comments
In summary, he felt that both dextro-amphetamine
(Dexedrine) and Temazepam (Restoril) were
extremely valuable medications during the war. He
strongly supports their continued availability for
future use as needed.
Squadron Pilots
Comments
Individual opinions of the pilots interviewed were
either positive or neutral. None expressed a negative
opinion regarding the availability or use of either drug.
Several members were adamant that the squadron
could not have maintained its level of flight
operations without the medications they used. Those
who didn’t see any personal benefit still endorsed
having it available for others in the squadron.
Operations Officer’s
Comments
(Navy Exective Officer Equivalent)
The OPSO felt that given the schedule flown the
squadron had the potential for “five to ten accidents”
yet none occurred. During some 24 hour periods crews
were airborne for thirteen to fourteen hours with a
maximum of six to eight hours off before the next days
flying began. An attempt was made to schedule pilots
to fly morning, afternoon then night flight on
consecutive days to reduce fatigue. The level
of manning did not allow as much
flexibility as desired. Overall, he felt that
“pilots do not like to take drugs” but
that in reference to these
medications the squadron
“just had to have it.”
Commanding Officer’s
Comments
The commanding officer
required all pilots to carry
Dexedrine on every flight.
Personally, he only used the
stimulant during the
TRANSPAC when he felt he would
have fallen asleep. While in-theater he
carried the go-pills on every flight but
never took any. He didn’t encourage his
pilot’s to use the medication but considered it a
safety-of flight issue. If they didn’t need anything
he discouraged its use. He was not aware of any abuse
or a “run on the pharmacy.” Prior to approving use he
discussed the issue with the wing commander who also
carried the medication in the airplane.
In his opinion,
the main benefit of the medications
was to increase or maintain the margin of safety
during extremely heavy flight operations. He stated
that the level of tasking was not increased based on the
use of any medications. When asked about squadron
manning he said that 1.25 pilots/aircraft was about right
given the normal peacetime funding for training but
needed to be increased for combat operations.
His comments on supervision
of the aircrew included
that “you must give them guidelines and then let
them self-regulate. If you can’t trust them with the
medication then you can’t trust them with a 50
million dollar airplane to try and go kill someone.”
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