Acclimatisation, Acute Mountain Sickness and HAPE

Based on non-trivial medical events, an altitude of 3000 m or more is considered high altitude (HA) although significant individual susceptibility occurs at 2500 m. More than 45 million permanent or nomadic population is estimated to live above 3000 m scattered across 12 mountains and plateaus in all continents. A very large number of lowlanders visit HA for tourism, sports or professional purposes and constitute a high-risk group.

A subtle-to-gross change at multiple biochemical and functional levels takes place at HA. The changes correlate roughly with altitude and rate of ascent of a person and are influenced by a number of collateral factors, controllable or uncontrollable. Lack of or slow acclimatisation, non-specific appetite loss followed by weight loss, acute and chronic mountain sickness, high altitude pulmonary edema (HAPE), high altitude cerebral edema (HACE), cold injuries, and diseases secondary to thromboembolic phenomenon (and their complex interplay) have been recognised as major pathological entities at HA. DRDO has done pioneering work in understanding the basic issues involved and developing medical strategies to combat these problems. It involves both allopathic and alternative/traditional methods of treatment. DIPAS has done extensive work on pathophysiologic changes associated with HA and their correction using micronutrients, nitric oxide, glutamic acid and several herbal products. To compliment the ongoing activities under the same umbrella, INMAS has now initiated a multi-pronged programme having diagnostic and therapeutic components using allopathic system of medicine. Based primarily on nuclear medicine technology, several diagnostic methodologies and drug formulations have been developed that have direct relevance for HA medicine.
 

DRDO has made some original observations that are important for residents at HA including defence and paramilitary forces after undertaking the largest global pulse oximetry survey. Besides creating a large databank serving as a reference at different altitudes, it was found that a new inductee has a higher heart rate and lower blood oxygen level compared to the natives, which only gets partially corrected during acclimatisation at extreme heights. Age, physical fitness, genetics, but not gender of a new entrant has a bearing on blood oxygen level. Among highlanders, different ethnic groups may have different basal oxygen levels. Surprisingly, basal heart rate is significantly lower in most adapted ethnic groups, who also may have highest exercise capacity. Highlander infants have significantly lower blood oxygen, a fact that can have anthropologic and recruitment significance. Clubbing is common in elders suggesting chronic hypoxemia.

Acclimatisation appears to follow circadian cycle and may be a 'night-time' phenomenon. Food, postural and exercise response gets more abnormal with altitude in non-acclimatised personnel and more so in acute mountain sickness (AMS). Blood oxygen level deteriorates drastically in any individual after a critical altitude

        SaO2        Heart Rate
Pulse oximetry data : Symptomatic vs asymptomatic

inductees at 13500 feet

suggesting interstitial/pulmonary edema. Even at moderate altitudes,
a large number of inductees may have ‘sub-clinical' AMS or HAPE, which gets better with time, but often goes unreported. It is

important to identify such personnel, as their work efficiency would be quite poor though they might appear medically fit. The survey confirms absence of complete acclimatisation beyond a critical altitude.

 

Simple Diagnostic Protocols for AMS & HAPE Susceptibility

Hypoxemia at rest correlates with mountain sickness with high specificity but low sensitivity. Non-acclimatisation can also a be judged objectively by person's response to food and beverage intake, postural changes, physical stress and sleep.

DRDO has introduced a simple non-invasive test, exercise provoked pulse oximetry (EPPO), that may be used to segregate asymptomatic inductees into 'normal', 'non-acclimatised',

'susceptible to benign mountain sickness' and ‘susceptible to malignant mountain sickness' categories with high sensitivity. This concept is based on initial pilot studies. Critical values of EPPO are being defined by collecting more data. The test  can also be used with obvious

                    Normal               Probable/PHT        Probable AMS    Probable HAPE
                                        Non-acclimatisation

     

 advantages in assessing medical fitness of soldiers at HA. Two new pathology terms and a new simple mathematical parameter have been introduced that may quantitatively define 'acclimatisation', 'medical fitness', and to AMS' and make comparisons easy to assess improvement or deterioration of mountain sickness objectively.
 

Preventive & Treatment Protocols for AMS, HAPE, & HACE

Simple changes in lifestyle of inductees in terms of food, posture, and physical and respiratory exercises can help them to acclimatise faster and arrest complications. The same is true for residents at extreme altitude. Medical management of altitude-related symptoms and diseases may now include glycerol, mannitol, prokinetic agents, and antiplatelet agents in an appropriate subgroup of patients.

ITAD
DRDO has introduced a novel concept inhalation therapy for alveolar deposition (ITAD) for treating cases with pulmonary hypertention, AMS, HAPE and HACE. Using a simple delivery system, Anukool, developed at INMAS, ITAD therapy can also be given at field level even by non-medical personnel. More than 150 personnel have undergone the therapy, majority of whom were defence personnel. The treatment has been successfully performed at Referral & Research Army Hospital, Delhi; District Hospital, Keylong; and District Hospital, Leh; Badrinath Shrine Trust Hospital, Chamoli, Uttaranchal, and at various stations in Ladakh and upper Himachal with participation of the district and army authorities. The 14 Corps is currently using the systems developed by DRDO at many places, including Siachen Hospital.  DRDO has already introduced nitric oxide therapy (more appropriate for hospital-based patients) and HAPO bags (more appropriate for on-the-spot emergency management) for HAPE patients. ITAD therapy is appropriate in the field conditions as well as for hospitals, both as an

emergency measure and maintenance therapy. The frequency and severity of this frequently fatal condition is expected to come down significantly using these approaches.
 
Anukool Drug Delivery System
 

ITAD acts by increasing pulmonary circulation, reducing pulmonary hypertension and increasing oxygen transport across the lung. A 20 per cent reduction in pulmonary hypertension, 5-15 per cent increase in blood oxygen and similar reduction in heart rate causes correction of cardio-pulmonary stress and improves mountain sickness and other diseases with similar pathology. This is possible due to preferred drug deposition in the alveoli using Anukool system. Drug deposition with commercial systems occurs in oropharynx and broncho-tracheal region making these unsuitable for use in HAPE and AMS.

Anukool drug-delivery system is a simple nebuliser-based equipment that works on re-entry principle. When connected between the aerosol generator and the mouthpiece, it changes AMAD features of the aerosols in such a way that it favours its deposition in the lung periphery rather than the central regions. This causes enhanced local effect of the drug and minimal systemic effect.  The system is cheap enough for widespread use at HA.
Safety and beneficial effects of ITAD therapy and Anukool delivery system have been validated using nuclear medicine imaging and ECHO facilities at INMAS and animal trial at DIPAS before conducting field trials in collaboration with 14 Corps

Salient Features
  • Twenty per cent reduction in pulmonary hypertension

  • Fifteen per cent improvement in blood oxygen and heart rate

  • Improved exercise tolerance at HA

  • Early response in AMS/HAPE

  • Safe, easy and cost-effective technology