James M. Vanderploeg

Pharmacokinetics and Oral Bioavailability of Scopolamine in Normal Subjects

The pharmacokinetics and bioavailability of scopolamine were evaluated in six healthy male subjects receiving 0.4 mg of the drug by either oral or intravenous administration. Plasma and urine samples were analyzed using a radioreceptor binding assay. After iv administration, scopolamine concentrations in the plasma declined in a biexponential fashion, with a rapid distribution phase and a comparatively slow elimination phase. Mean and SE values for volume of distribution, systemic clearance, and renal clearance were 1.4 ± 0.3 liters/kg, 65.3 ± 5.2 liters/hr, and 4.2 ± 1.4 liters/hr, respectively. Mean peak plasma concentrations were 2909.8 ± 240.9 pg/ml following iv administration and 528.6 ± 109.4 pg/ml following oral administration. Elimination half-life of the drug was 4.5 ± 1.7 hr. Bioavailability of the oral dose was variable among subjects, ranging between 10.7 and 48.2%. The variability in absorption and poor bioavailability of oral scopolamine indicate that this route of administration may not be reliable and effective.

Tolerance of centrifuge-simulated suborbital spaceflight by medical condition.

INTRODUCTION We examined responses of volunteers with known medical disease to G forces in a centrifuge to evaluate how potential commercial spaceflight participants (SFPs) might tolerate the forces of spaceflight despite significant medical history. METHODS Volunteers were recruited based upon suitability for each of five disease categories (hypertension, cardiovascular disease, diabetes, lung disease, back or neck problems) or a control group. Subjects underwent seven centrifuge runs over 2 d. Day 1 consisted of two +G(z) runs (peak = +3.5 G(z), Run 2) and two +G(x), runs (peak = +6.0 G(x), Run 4). Day 2 consisted of three runs approximating suborbital spaceflight profiles (combined +G(x) and +G(z), peak = +6.0 G(x)/+4.0 G(z)). Data collected included blood pressure, electrocardiogram, pulse oximetry, neurovestibular exams, and post-run questionnaires regarding motion sickness, disorientation, grayout, and other symptoms. RESULTS A total of 335 subjects registered for participation, of which 86 (63 men, 23 women, age 20-78 yr) participated in centrifuge trials. The most common causes for disqualification were weight and severe and uncontrolled medical or psychiatric disease. Five subjects voluntarily withdrew from the second day of testing: three for anxiety reasons, one for back strain, and one for time constraints. Maximum hemodynamic values recorded included HR of 192 bpm, systolic BP of 217 mmHg, and diastolic BP of 144 mmHg. Common subjective complaints included grayout (69%), nausea (20%), and chest discomfort (6%). Despite their medical history, no subject experienced significant adverse physiological responses to centrifuge profiles. DISCUSSION These results suggest that most individuals with well-controlled medical conditions can withstand acceleration forces of launch and re-entry profiles of current commercial spaceflight vehicles.

Sustained accelerated idioventricular rhythm in a centrifuge-simulated suborbital spaceflight

INTRODUCTION Hypergravitational exposures during human centrifugation are known to provoke dysrhythmias, including sinus dysrhythmias/tachycardias, premature atrial/ventricular contractions, and even atrial fibrillations or flutter patterns. However, events are generally short-lived and resolve rapidly after cessation of acceleration. This case report describes a prolonged ectopic ventricular rhythm in response to high G exposure. CASE REPORT A previously healthy 30-yr-old man voluntarily participated in centrifuge trials as a part of a larger study, experiencing a total of 7 centrifuge runs over 48 h. Day 1 consisted of two +Gz runs (peak +3.5 Gz, run 2) and two +Gx runs (peak +6.0 Gx, run 4). Day 2 consisted of three runs approximating suborbital spaceflight profiles (combined +Gx and +Gz). Hemodynamic data collected included blood pressure, heart rate, and continuous three-lead electrocardiogram. Following the final acceleration exposure of the last Day 2 run (peak +4.5 Gx and +4.0 Gz combined, resultant +6.0 G), during a period of idle resting centrifuge activity (resultant vector +1.4 G), the subject demonstrated a marked change in his three-lead electrocardiogram from normal sinus rhythm to a wide-complex ectopic ventricular rhythm at a rate of 91-95 bpm, consistent with an accelerated idioventricular rhythm (AIVR). This rhythm was sustained for 2 m, 24 s before reversion to normal sinus. The subject reported no adverse symptoms during this time. DISCUSSION While prolonged, the dysrhythmia was asymptomatic and self-limited. AIVR is likely a physiological response to acceleration and can be managed conservatively. Vigilance is needed to ensure that AIVR is correctly distinguished from other, malignant rhythms to avoid inappropriate treatment and negative operational impacts.Suresh R, Blue RS, Mathers C, Castleberry TL, Vanderploeg JM. Sustained accelerated idioventricular rhythm in a centrifuge-simulated suborbital spaceflight. Aerosp Med Hum Perform. 2017; 88(8):789-793.

Tolerance of centrifuge-simulated suborbital spaceflight in subjects with implanted insulin pumps.

INTRODUCTION With commercial spaceflight comes the possibility of spaceflight participants (SFPs) with significant medical conditions. Those with previously untested medical conditions, such as diabetes mellitus (DM) and the use of indwelling medical devices, represent a unique challenge. It is unclear how SFPs with such devices will react to the stresses of spaceflight. This case report describes two subjects with Type I DM using insulin pumps who underwent simulated dynamic phases of spaceflight via centrifuge G force exposure. CASE REPORT Two Type I diabetic subjects with indwelling Humalog insulin pumps, a 23-yr-old man averaging 50 u of Humalog daily and a 27-yr-old man averaging 60 u of Humalog daily, underwent seven centrifuge runs over 48 h. Day 1 consisted of two +Gz runs (peak = +3.5 Gz, run 2) and two +Gx runs (peak = +6.0 Gx, run 4). Day 2 consisted of three runs approximating suborbital spaceflight profiles (combined +Gx and +Gz). Data collected included blood pressure, electrocardiogram, pulse oximetry, neurovestibular evaluation, and questionnaires regarding motion sickness, disorientation, greyout, and other symptoms. Neither subject experienced adverse clinical responses to the centrifuge exposure. Both maintained blood glucose levels between 110-206 mg · dl(-1). DISCUSSION Potential risks to SFPs with insulin pump dependent DM include hypo/hyperglycemia, pump damage, neurovestibular dysfunction, skin breakdown, and abnormal stress responses. A search of prior literature did not reveal any previous studies of individuals with DM on insulin pumps exposed to prolonged accelerations. These cases suggest that individuals with conditions dependent on continuous medication delivery might tolerate the accelerations anticipated for commercial spaceflight.

Centrifuge-Simulated Suborbital Spaceflight in a Subject with Cardiac Malformation.

INTRODUCTION Commercial spaceflight participants (SFPs) will introduce new medical challenges to the aerospace community, with unique medical conditions never before exposed to the space environment. This is a case report regarding the response of a subject with multiple cardiac malformations, including aortic insufficiency, pulmonary atresia, pulmonary valve replacement, ventricular septal defect (post-repair), and pulmonary artery stenosis (post-dilation), to centrifuge acceleration simulating suborbital flight. CASE REPORT A 23-yr-old man with a history of multiple congenital cardiac malformations underwent seven centrifuge runs over 2 d. Day 1 consisted of two +G(z) runs (peak = +3.5 G(z), run 2) and two +G(x) runs (peak = +6.0 G(x), run 4). Day 2 consisted of three runs approximating suborbital spaceflight profiles (combined +G(x) and +G(z)). Data collected included blood pressure, electrocardiogram, pulse oximetry, neurovestibular exams, and post-run questionnaires regarding motion sickness, disorientation, greyout, and other symptoms. Despite the subjects significant medical history, he tolerated the acceleration profiles well and demonstrated no significant abnormal physiological responses. DISCUSSION Potential risks to SFPs with aortic insufficiency, artificial heart valves, or valvular insufficiency include lower +G(z) tolerance, earlier symptom onset, and ineffective mitigation strategies such as anti-G straining maneuvers. There are no prior studies of prolonged accelerations approximating spaceflight in such individuals. This case demonstrates tolerance of acceleration profiles in an otherwise young and healthy individual with significant cardiac malformations, suggesting that such conditions may not necessarily preclude participation in commercial spaceflight.

Preflight screening techniques for centrifuge-simulated suborbital spaceflight

INTRODUCTION Historically, space has been the venue of the healthy individual. With the advent of commercial spaceflight, we face the novel prospect of routinely exposing spaceflight participants (SPFs) with multiple comorbidities to the space environment. Preflight screening procedures must be developed to identify those individuals at increased risk during flight. We examined the responses of volunteers to centrifuge accelerations mimicking commercial suborbital spaceflight profiles to evaluate how potential SFPs might tolerate such forces. We evaluated our screening process for medical approval of subjects for centrifuge participation for applicability to commercial spaceflight operations. METHODS All registered subjects completed a medical questionnaire, physical examination, and electrocardiogram. Subjects with identified concerns including cardiopulmonary disease, hypertension, and diabetes were required to provide documentation of their conditions. RESULTS There were 335 subjects who registered for the study, 124 who completed all prescreening, and 86 subjects who participated in centrifuge trials. Due to prior medical history, five subjects were disqualified, most commonly for psychiatric reasons or uncontrolled medical conditions. Of the subjects approved, four individuals experienced abnormal physiological responses to centrifuge profiles, including one back strain and three with anxiety reactions. DISCUSSION The screening methods used were judged to be sufficient to identify individuals physically capable of tolerating simulated suborbital flight. Improved methods will be needed to identify susceptibility to anxiety reactions. While severe or uncontrolled disease was excluded, many subjects successfully participated in centrifuge trials despite medical histories of disease that are disqualifying under historical spaceflight screening regimes. Such screening techniques are applicable for use in future commercial spaceflight operations.

Subject anxiety and psychological considerations for centrifuge-simulated suborbital spaceflight.

INTRODUCTION Anxiety and psychological concerns may pose a challenge to future commercial spaceflight. To help identify potential measures of anxiousness and indicators of flight-related stress, the psychiatric histories and anxiousness responses of volunteers exposed to G forces in centrifuge-simulated spaceflight acceleration profiles were examined. METHODS Over 2 d, 86 individuals (63 men, 23 women), 20-78 yr old, underwent up to 7 centrifuge runs. Day 1 consisted of two +G(z) runs (peak = +3.5 G(z)) and two +Gx runs (peak = +6.0 G(x)). Day 2 consisted of three runs approximating suborbital spaceflight profiles (combined +G(x) and +G(z)). Hemodynamic data were collected during the profiles. Subjects completed a retrospective self-report anxiety questionnaire. Medical monitors identified individuals exhibiting varying degrees of anxiousness during centrifuge exposure, medical histories of psychiatric disease, and other potential indicators of psychological intolerance of spaceflight. RESULTS The retrospective survey identified 18 individuals self-reporting anxiousness, commonly related to unfamiliarity with centrifuge acceleration and concerns regarding medical history. There were 12 individuals (5 men, 7 women, average age 46.2 yr) who were observed to have anxiety that interfered with their ability to complete training; of these, 4 reported anxiousness on their questionnaire and 9 ultimately completed the centrifuge profiles. Psychiatric history was not significantly associated with anxious symptoms. DISCUSSION Anxiety is likely to be a relevant and potentially disabling problem for commercial spaceflight participants; however, positive psychiatric history and self-reported symptoms did not predict anxiety during centrifuge performance. Symptoms of anxiousness can often be ameliorated through training and coaching. Even highly anxious individuals are likely capable of tolerating commercial spaceflight.

An emergency medical planning guide for commercial spaceflight events

BACKGROUND Commercial spaceflight events transporting paying passengers into space will begin to take place at various spaceports around the country within the next few years. Many spaceports are located in remote areas that are far from major hospitals and trauma centers. Spaceport medical directors should develop emergency medical plans (EMPs) to prepare for potential medical contingencies that may occur during commercial spaceflight events. The aim of this article is to guide spaceport medical directors in emergency medical planning for commercial spaceflight events. METHODS This guide is based on our experience and a recently developed EMP for Spaceport America which incorporated a literature review of mass gathering medicine, existing planning guides for mass gathering events, and EMPs for analogous aerospace events. RESULTS We propose a multipronged approach to emergency medical planning, consisting of event planning, medical reconnaissance, medical personnel, protocols, physical facility and hardware, and documentation. DISCUSSION Medical directors should use this guide to develop an emergency medical plan tailored to the resources and constraints specific to their events.

Screening and Mitigation of Layperson Anxiety in Aerospace Environments

INTRODUCTION Anxiety may present challenges for commercial spaceflight operations, as little is known regarding the psychological effects of spaceflight on laypersons. A recent investigation evaluated measures of anxiety during centrifuge-simulated suborbital commercial spaceflight, highlighting the potential for severe anxiousness to interrupt spaceflight operations. METHODS To pave the way for future research, an extensive literature review identified existing knowledge that may contribute to formation of interventions for anxiety in commercial spaceflight. Useful literature was identified regarding anxiety from a variety of fields, including centrifugation, fear of flying, motion sickness, and military operations. RESULTS Fear of flying is the most extensively studied area, with some supportive evidence from centrifugation studies. Virtual reality exposure (VRE) is as effective as actual training flight exposure (or analog exposure) in mitigation of flight-related anxiety. The addition of other modalities, such as cognitive behavioral therapy or biofeedback, to VRE improves desensitization compared to VRE alone. Motion sickness-susceptible individuals demonstrate higher trait anxiety than nonsusceptible individuals; for this reason, motion sickness susceptibility questionnaires may be useful measures to identify at-risk individuals. Some military studies indicate that psychiatric history and personality classification may have predictive value in future research. Medication countermeasures consisting of benzodiazepines may quell in-flight anxiety, but do not likely improve anxiety on repeat exposure. DISCUSSION The scarce available literature addressing anxiety in unique environments indicates that training/repeated exposure may mitigate anxiety. Anxiety and personality indices may be helpful screening tools, while pharmaceuticals may be useful countermeasures when needed. Mulcahy RA, Blue RS, Vardiman JL, Castleberry TL, Vanderploeg JM. Screening and mitigation of layperson anxiety in aerospace environments. Aerosp Med Hum Perform. 2016; 87(10):882-889.

Implanted medical devices in the radiation environment of commercial spaceflight.

INTRODUCTION Some commercial spaceflight participants (SFPs) may have medical conditions that require implanted medical devices (IMDs), such as cardiac pacemakers, defibrillators, insulin pumps, or similar electronic devices. The effect of space radiation on the function of IMDs is unknown. This review will identify known effects of terrestrial and aviation electromagnetic interference (EMI) and radiation on IMDs in order to provide insight into the potential effects of radiation exposures in the space environment. METHODS A systematic literature review was conducted on available literature on human studies involving the effects of EMI as well as diagnostic and therapeutic radiation on IMDs. RESULTS The literature review identified potential transient effects from EMI and diagnostic radiation levels as low as 10 mGy on IMDs. High-energy, therapeutic, ionizing radiation can cause more permanent device malfunctions at doses as low as 40 mGy. Radiation doses from suborbital flight altitudes and durations are anticipated to be less than those experienced during an average round-trip, cross-country airline flight and are unlikely to result in significant detriment, though longer, orbital flights may expose SFPs to doses potentially harmful to IMD function. DISCUSSION Individuals with IMDs should experience few, if any, radiation-related device malfunctions during suborbital flight, but could have problems with radiation exposures associated with longer, orbital flights.