Antihypertensives in Fighter Flying: IAF Experience

Hypertension: Potential hazards & aeromedical implications

Hypertension, the most prevalent risk factor for arterial disease in the industrialized world [1], is a frequently encountered clinical condition among the aircrew. Arterial systolic and diastolic blood pressures are continuous variables that can be influenced by a host of extraneous factors. It is an established fact that various physiological factors viz. stress, anxiety, exercise, diet, posture, ambient temperature etc can elevate blood pressure even in the absence of any organic pathology.

The Eighth report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC-8) offers excellent background information as well as recommendations for classification, risk stratification and therapy. It mentions that ‘Pre-hypertension’ is not a disease, but it identifies those who are likely to progress to Stage 1 or Stage 2 HTN in the future [3, 4]. This classification of hypertension is listed in Table 1 below:

Diagnosis of HTN should be based on atleast three blood pressure readings taken on different days. Attempts should be made to measure the blood pressure in controlled and standardized conditions [5]. Evidence from clinical trials indicate that antihypertensive medications should be initiated in patients less than 60 years old if the systolic BP is persistently >140 mmHg and the diastolic BP is persistently >90 mmHg despite non-pharmacological therapy [6, 7]. The existing aeromedical guidelines of the organisation mandate absence of target organ damage viz., hypertensive retinopathy, hypertensive nephropathy etc for categorizing an aviator in Stage I HTN.

24-hour Ambulatory Blood Pressure Monitoring (ABPM), is the best tool to rule out White coat HTN, but is not being used extensively as a diagnostic tool at present. Number of studies have supported the use of ABPM for assessing the risk of coronary events [8, 9]; any deviation from the normal pattern of BP fall or/ ‘dipping’, during sleep significantly aggravates the risk [9]. White coat HTN could be relatively benign in the short term [9] but studies have shown that it is of high concern for long-term risk of developing sustained HTN [10, 11]. Systolic BP is considered as powerful risk predictor than diastolic BP. It has been estimated that for each 10 mmHg rise in systolic BP, there is an associated 30% increase in coronary mortality risk. The cardiovascular diseases have been ascribed as the single most common medical cause for termination of career in civil aviation industry as well [12]. Reassuringly, numerous therapeutic trials have demonstrated that effective treatment of HTN reduces the risk substantially and relatively rapidly [13]. The effect of treatment is greatest and realized most rapidly for stroke, but there is also good evidence for a reduction in coronary events of the order of at least 25 per cent with effective management of hypertension [5].

With the change in the life style and increasing trend of ‘Metabolic syndrome’, constant medical review of aircrew is deemed essential. Fighter flying being quite strenuous and requiring very high level of fitness, a further cautious approach is required for permitting a pilot to fly in the high risk environment with a clinical condition like this. Long term use of antihypertensive medications, their adverse effects, especially in flying environment needs to be monitored at regular intervals to reduce the risk of sudden in-flight incapacitation.

Antihypertensive drugs for fighter flying: Desired qualities

The antihypertensive drugs should have following desirable qualities to make them compatible for fighter flying:

1. To be administered by oral route only

2. Devoid of side effects that may cause distraction during flying viz. itching, nausea, headache etc.

3. It should not compromise sensory, motor, coordinative, basal ganglionic and higher mental functions.

4. It should not compromise +Gz tolerance, cardiovascular and autonomic reflexes involved in maintenance of blood pressure during G exposure.

Commonly prescribed antihypertensive drugs: Aeromedical implications

1. Diuretics: Diuretics are considered as a very safe class of drugs. However, in some instances it is known to cause hypokalemia induced cardiac arrhythmias besides causing increased frequency of urination. Loop diuretics cause hypokalemia more commonly and to a larger extent as compared to thiazide diuretics [14]; hence loop diuretics are not compatible with the aviation duties while thiazide can be permitted for flying only if serum potassium levels are monitored frequently and timing of the drug intake is such that diuretic effect is during non-flying hours. Carbonic anhydrase inhibitors due to lower potency and uncommon oral use are not permitted in fighter flying.

2. Angiotensin Converting Enzyme (ACE) inhibitors: ACE inhibitors are widely used in general population as well as flying due to their safety record. The only side effect is dry cough (rarely) which does not affect all people and hence unlikely to be a major cause of concern [15]. Few studies on fighter aircrew have suggested that they can reduce +Gz tolerance [16]. However, this has not been borne out in actual practice.

3. Angiotensin Receptor Blockers (ARBs): ARBs are also considered as a safe class of antihypertensives due to their negligible side effects. They have shown efficacy which is comparable to ACE inhibitors but avoid the side effects such as cough [17]. Except for uricosuria with Losartan, they appear to have neutral metabolic effects as well [18]. They are unlikely to reduce +Gz tolerance and are thus permitted for fighter flying.

4. Calcium Channel Blockers (CCBs): CCBs are not permitted in fighter flying as they cause direct relaxation of vascular tone and thus affect the +Gz tolerance of the aircrew.

5. Sympatholytics: Alpha blockers carry significant risk of postural drop in BP, thus likely to reduce +Gz tolerance. Beta blockers reduce HR, hence decrease cardiac output and in addition it is known to cause fatigue and impotence. Due to significant vasodilator effect, it can also cause reduction in +Gz tolerance. Such a profile of adverse effects makes this class of antihypertensives a poor choice for aviators [15].

6. Alpha 2 agonist: This group of drug is not permitted in fighter flying due to potential side effects viz., sedation, drowsiness, depression, degradation of psychomotor performance etc [19].

7. Other classes (Direct vasodilators, Ganglion blockers, Potassium channel openers, Renin inhibitors): These group of antihypertensives are also not permitted in fighter flying due to potential side effects and uncommon oral use.

Thus, the recommended drugs which can be prescribed for fighter aircrew includes Thiazide diuretics, ACE inhibitors and ARBs only.

International considerations

The USAF has permitted unrestricted high performance aircraft flying with use of single drug from the group of diuretics (Thiazide with/ without Triamterene), ACE inhibitors (Lisinopril or Ramipril) and ARBs (Losartan or Telmisartan) [20]. Concerns that ACE inhibitors might have an adverse effect on +Gz tolerance have not been borne out by experience in the US Air Force [21]. With ACE inhibitor (Lisinopril), aviator flying high performance aircraft needs to undergo centrifuge testing as soon as possible once BP is controlled [21]. The US Navy accepts these agents for high performance aircraft flying without mentioning the requirement of G-tolerance testing [22].

IAF guidelines

The IAF has permitted fighter aircrew to fly on antihypertensive medications which includes Thiazide diuretics, Thiazide type diuretics, ACE inhibitors (e.g. Enalapril 20 mg/ day: max dose) and ARBs. The laid down guidelines for evaluation, treatment and disposal of hypertensive fighter aircrew includes nonpharmacological remedies viz. dietary modifications like salt & alcohol restriction, weight reduction and regular exercise with careful evaluation during annual medical examinations for pre-hypertension class. However, aircrew with Stage I HTN without any co-morbidities, any target organ damage and on single drug therapy can be upgraded to restricted flying category after initial observation in ground category for 12 weeks to observe for any side effects and idiosyncratic reactions. Prior to the upgradation, BP should be well controlled on medications without any evidence of side effects of the drug and the aircrew should have successfully completed the High G training profile in centrifuge at IAM, Bangalore. This High G training profile includes centrifuge exposure at 9G for five seconds. Subsequently the aircrew can be further upgraded to almost full flying category. Thereafter, the aircrew is recommended for annual review by Medicine specialist / Cardiologist for next five years at one of the nodal medical evaluation centre only. Since, Stage II HTN cases require combination/ multi drug therapy, hence they are deemed unfit for fighter flying.

Need for centrifuge run before return to cockpit

Diuretics are known to cause hypokalaemia which may result in cardiac arrhythmia, especially on exposure to +Gz stress. However, the chance of hypokalemia with Thiazide or/ Thiazide type diuretics is remote. Studies have also suggested that ACE inhibitors can reduce +Gz tolerance thus affecting the aviator’s capability to withstand the +Gz stress. Hence, a check for G tolerance and endurance would be deemed appropriate for all cases on antihypertensives prior to declaring them fit for the fighter cockpit [5]. At present, IAF database on the detailed effects of drugs under high +Gz conditions is lagging due to small sample size. It is worth mentioning that the response of drugs may vary with ethnicity and genetic predisposition. Thus, it is prudent to progress with an evidence based approach by assessing the G tolerance and the response of drugs under high G stress in Indian ethnic group before declaring them fit for fighter cockpit. The successful completion of 9G for five seconds ensures that the aircrew is at par with their drug free counterparts.

Our Experience

Since the inception of this policy IAM has evaluated 11 fighter pilots with Essential HTN till Jun 2016. The descriptive analysis of these cases is presented in Table 2 below:

Amongst eleven fighter aircrew with potential for upgradation, two aircrew were not subjected to centrifuge run due to associated co-morbidities (DM type 2, CSOM with TM perforation) while one could not complete the required run due to fatigue and unwillingness and was thus declared unfit for fighters. Rest eight fighter aircrew who were subjected to centrifuge evaluation successfully achieved the required target of 9G for five seconds (Fig 1).

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Fig 1.

Upgradation to fighter stream

* Two pilots were not subjected to centrifuge run due to associated comorbidities and one pilot was unwilling for completing the target profile

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The detailed analysis of the available data revealed that there is a higher prevalence of HTN in senior group of participants while overweight was found to be higher in relatively younger subjects. Dyslipidemia (27.3%), DM (9.1%) and overweight (36%) (18% overweight alone + 18% overweight with comorbidities) were found to be the associated co-morbidities. All the aircrew were advised life style modifications along with anti-hypertensive medications for optimal pharmacological outcome. Details of metabolic profile during upgradation is presented in Table 3 while Fig 2 depicts the prescribed antihypertensive medications.

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Fig 2.

Prescribed antihypertensive drugs

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Co-morbidities in the aircrew are shown in Fig 3 while Fig 4 depicts the change of antihypertensives for fighter compatibility.

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Fig 3.

Co-morbidities

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Fig 4.

Change of antihypertensives for fighter compatibility

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