Influences of Hyperbaric Oxygen on Blood Pressure, Heart Rate and Blood Glucose Levels in Patients with Diabetes Mellitus and Hypertension
- Noori S. Al-Waili
, 
, - Glenn J. Butler,
- Jorge Beale,
- Mahdi S. Abdullah,
- Michael Finkelstein,
- Michael Merrow,
- Richard Rivera,
- Richard Petrillo,
- Zev Carrey,
- Bok Lee,
- Michael Allen
- Life Support Technologies, Inc., NEWT Technologies, Inc., Chronic Wound Treatment and Hyperbaric Medicine Center, The Mount Vernon Hospital, Sound Shore Health System, New York Medical College, New York, NY
- Received 19 December 2005
- Accepted 11 May 2006
- Available online 10 October 2006
- (ARCMED-D-05-00517)
Background
We investigated the influences of hyperbaric oxygen (HBO2) on systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) and blood glucose level (BGL).
Methods
Forty one patients with hypertension (HTN), diabetes mellitus (DM), HTN and DM and/or no HTN or DM underwent HBO2 sessions (15–40 sessions for each patient). SBP, DBP, HR and BGL (for diabetics) were recorded before and after each session.
Results
HBO2 caused significant elevation in SBP (11%) and DBP (12%) and a decrease in HR (18%) (p <0.001). Patients with DM and HTN showed higher elevation in SBP and DBP. HBO2 lowered BGL by 23% (p <0.001). When basal BGL was in the range of 120–170 mg/dl, it dropped to <100 mg/dl in 31/60 treatment sessions (52%). When basal BGL was <120 mg/dl it dropped to <70 mg/dl in 8/34 sessions. There was a possibility of lowered BGL when basal BGL was <170 mg/dl and a marked reduction in BGL occurred when basal BGL was <120 mg/dl. HBO2 caused a marked elevation in SBP and DBP when basal SBP was >140 mmHg. Critical elevation was obtained when SBP was >160 mmHg. The use of beta blockers caused significant elevation of blood pressure while reducing HR.
Conclusions
HBO2 causes elevation of blood pressure and lowering of HR and BGL, which were augmented in the presence of HTN, DM, or beta blocker. The use of beta blockers for the management of HTN should be avoided during HBO2 therapy.
Key Words
- Hyperbaric;
- Heart rate;
- Glucose;
- Diabetes;
- Hypertension;
- Beta blocker;
- Oxygen
Introduction
HBO2 means breathing pure (100%) oxygen while in a chamber at increased ambient pressure. Treatment is administered using monoplace chambers that accommodate one individual usually in the supine position, or multiplace chambers that accommodate two or more patients. HBO2 has been shown to be safe with few complications (1). Center for Medicare and Medicaid Services (CMS) following the recommendations of the Undersea and Hyperbaric Medical Society (UHMS) has approved use of HBO2 for several indications. These include acute carbon monoxide poisoning, decompression sickness, gas embolism, gas gangrene, acute traumatic peripheral ischemia, crush injuries and suturing of severed limbs, progressive necrotizing infections, acute peripheral arterial insufficiency, preservation of compromised skin grafts, chronic refractory osteomyelitis, osteoradionecrosis, soft tissue radionecrosis, cyanide poisoning actinomycosis and diabetic wounds of the lower extremity. Research, however, into the effectiveness of HBO2 for a number of other conditions is ongoing 2, 3, 4 and 5.
HBO2 increases parasympathetic activity and endothelin-1 activity in divers and healthy volunteers 6, 7 and 8. It increases catecholamines and thromboxane B2 and induces vasoconstriction 10, 11 and 12. In chronic heart failure, HBO2 reduces aldosterone secretion and renin secretion rate (13). In rats, HBO2 elevated SBP and pulse pressure, while mean arterial blood pressure remained unchanged 14 and 15.
HBO2 decreased HR in animals, divers and patients with ischemia of lower extremities 14, 15, 16 and 17. It elevates left ventricular pressure and contractility in rats (12). Diabetic patients may show fluctuation in BGL while receiving HBO2. HBO2 increases glucose utilization in the rat brain and stimulates residual insulin secretion in DM 18, 19 and 20. These neuronal and hormonal changes observed during HBO2 make close monitoring of BGL, blood pressure and HR an extremely important task to avoid possible complications. In this study we investigated the effects of HBO2 on SBP, DBP, HR and BGL in patients with HTN, DM, HTN and DM and in non-diabetic or non-hypertensive patients. Complications were monitored during and after each HBO2 session.
Patients and Methods
Patients
We studied 41 patients treated with HBO2 as part of their management for various indications (Table 1). There were 27 males and 14 females; ages ranged from 31 to 86 years (mean: 61 ± 14.6 years). The patients were referred to our Hyperbaric Unit (Life Support Technologies Group), Chronic Wound Treatment and Hyperbaric Medicine Center, The Mount Vernon Hospital, New York, from medical or surgical departments of the hospital and from other health facilities. The patients were divided into four groups for comparison: 1) hypertensive patients; 2) diabetic patients, 3) diabetic and hypertensive patients, and 4) patients who had no HTN or DM. The patients were closely observed for any side effects during the depressurization phase of the treatment and following completion of each treatment.
Table 1. Patients admitted for study
Variables Number Percentage Number of patients 41 Male 27 66 Female 14 34 Age Mean: 61 ± 14.6 (31−86) Associated diseases Hypertension 6 15 Diabetes mellitus 11 29 Hypertension and diabetes 12 29 No hypertension, no diabetes 12 29 Gout 2 5 Renal failure 1 2 Malignancy 8 20 Asthma 1 2 Valve replacement 1 2 Arthritis 1 2 Cerebrovascular accident 1 2 Depression 3 7 Hypothyroidism 2 5 DVD 1 2 Anemia 3 7 Glucoma 1 2 Treatment Hypertension: beta blockers 7/17 41 Diabetes mellitus: insulin 16/23 70 Indications for HBO2 Chronic osteomyelitis 16 39 Osteoradionecrosis 6 15 Necrotizing fasciitis 1 2 Compromised skin graft 6 15 Chronic ulcer 9 22 Nonhealed wound 4 10 - Full-size table
Treatment Protocol
Treatments were administered in a monoplace chamber (Environmental Tectonics Corporation, Southampton, PA) with the subject breathing 100% oxygen. Qualified technicians administered the HBO2. Specialist physicians in hyperbaric medicine were available during HBO2 treatment. Treatment protocol was 2.0–2.5 atmosphere pressure (ATA) for 60–90 min, according to the indication. Treatment was given one session per day from Monday to Friday. Compression was started after 15 min bed rest and 2.0–2.5 ATA was reached in 10–15 min. Patients remained in the supine position during each session. Number of treatment sessions was 15 to 30 for each patient. Data from 700 HBO2 treatment sessions were reviewed for SBP, DBP, HR, and BGL activity and recorded side effects.
Vital Signs and Blood Glucose Level Measurements
Basal supine blood pressure, HR and BGL measurements were made before depressurization and were repeated within 10 min following completion of each HBO2 treatment session. Blood pressure and HR were measured with use of an electronic monitor (Datascope Corp., Mohwash, NJ). BGL was measured electronically using the finger prick method (Professional Care Lifescan, Milpitas, CA). When basal BGL was <100 mg/dL, the patient was given juice or a sandwich before the session. Vital signs and BGL were measured after 15 min supine rest.
Statistical Analysis
Data were expressed as mean ± standard deviation. A paired and unpaired t-test was used to compare means before and after treatment for each patient and for each group. ANOVA test was used to compare means of the four groups. A probability value of <0.05 is statistically significant. An F test was used to evaluate the statistical significance of between-group differences. The F value is the measurement of distance between individual distributions. As F goes up, p goes down.
Results
Criteria for Patients
Table 1 shows the criteria for patients enrolled in the study. The most common indication for HBO2 in our patients was chronic osteomyelitis. Most of the patients had DM and HTN in addition to their health problem indicated for HBO2. Insulin and beta blockers were the main drugs used as part of their management for HTN and DM.
Effect of HBO2 on the Four Groups
Initially, blood pressure was significantly higher in patients with HTN and DM in comparison to other groups; F = 35, p <0.001 (Table 2). HBO2 caused a significant elevation in blood pressure and a significant decrease in HR. Greater elevation in blood pressure was obtained in patients with both HTN and DM. Diabetic patients showed higher elevation in blood pressure when compared to patients with HTN or non-diabetic, non-hypertensive patients. Patients with HTN and DM showed a lower drop in HR compared to other groups. In diabetics, HBO2 caused a significant drop in mean BGL approximately to the same extent in patients with DM alone or in patients with both DM and HTN.
Table 2. Mean (±SD) blood pressure, heart rate and blood glucose level before and after hyperbaric oxygen session
Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Heart rate (beats/min) Blood sugar (mg/dl) Groups (number of patients) Before HBO2 After HBO2 p value % Before HBO2 After HBO2 p value % Before HBO2 After HBO2 p value % Before HBO2 After HBO2 p value % Hypertensive patients (6) 127 ± 12.9 141 ± 10.9 0.001 11 73.3 ± 8.03 83.4 ± 7.9 <0.001 14 80.2 ± 10.5 68.1 ± 10.9 0.001 15 Hypertensive and diabetic patients (12) 136 ± 15.7 160 ± 22.2 0.001 18 74.1 ± 10.2 83.8 ± 10.1 0.001 13 83.5 ± 13.5 72 ± 12.2 0.001 14 234 ± 102 186 ± 94.7 0.001 21 Diabetic patients (11) 125± 15 142± 17.2 <0.001 14 71.8 ± 8.81 80.4 ± 7.8 <0.001 12 85.2 ± 12.2 71.4 ± 12.1 <0.001 16 236 ± 86.5 185 ± 76 0.001 22 No hypertension, no diabetes (12) 123 ± 12.1 136 ± 13.4 0.001 11 72.4 ± 6.8 80.8 ± 7.3 0.001 12 82.3 ± 9.8 67.8 ± 9.1 <0.001 18 Total patients (41) 127 ± 15.2 134 ± 10.6 0.001 6 72.9 ± 8.5 81.8 ± 8.6 <0.001 12 82.7 ± 11.7 69.3 ± 10.9 0.001 16 231 ± 95 179 ± 85.8 <0.001 23 - Full-size table
Effects of HBO2 on Non-hypertensive, Non-diabetic Patients
HBO2 caused a significant elevation in DBP and SBP and a significant drop in HR and BGL in 12 patients who had no DM or HTN. Four female non-diabetic, non-hypertensive patients had a greater elevation in blood pressure as compared to eight male non-diabetic, non-hypertensive patients (mean percent 15 vs. 11 for SBP and mean percent 19 vs. 14 for SBP). Male non-diabetic, non-hypertensive patients had a greater reduction in HR as compared to female non-diabetic, non-hypertensive patients (mean percent drop 19 vs. 16).
Effect of HBO2 on Hypertensive Patients
In six patients with HTN, the reduction in SBP ranged between 6 and 13% and in DBP ranged between 8 and 20%. The main effects appeared on the three patients who used beta blockers, showing greater elevation in blood pressure (mean percent 17 vs. 10 for DBP and mean percent 15 vs. 13 for SBP) and higher drop in HR (mean percent 17 vs. 13) compared to patients using other medications. With use of calcium antagonist, HBO2 caused a 22% reduction in HR, which was the highest reduction among the groups.
Effects of HBO2 on Diabetic Patients
Except for one female patient on insulin, HBO2 caused a significant elevation in SBP and DBP in the 11 patients with DM. A significant drop in BGL was observed in all patients. Eight male diabetic patients had higher mean percent elevation in SBP and DBP compared with three female diabetic patients (18 vs. 13% for SBP, and 15 vs. 8% for DBP). A greater drop in BGL was observed in male diabetic patients as compared to female diabetic patients (26 vs. 20%). Eight diabetic patients on insulin had a mean percent (25%) drop in BGL compared to three diabetic patients on oral anti-diabetics whose BGL dropped a mean of 23%.
Effects of HBO2 on Hypertensive and Diabetic Patients
Significant elevation in blood pressure and significant drop in HR and BGL were observed in patients with both HTN and DM. A greater elevation in blood pressure and drop in HR was observed in four patients using beta blockers compared to eight patients using other medication (mean percent 19 vs. 15 for SBP, 17 vs. 14 for DPB and 17 vs. 13 for HR). Seven female patients showed higher elevation in blood pressure and a greater drop in BGL compared with five male patients (mean percent 20 vs. 13 for SBP, 16 vs. 13 for DBP and 25 vs. 22 for BGL). Four patients using oral anti-diabetics had a mean percent (20%) drop in BGL as compared to seven patients on insulin whose BGL dropped a mean of 22%.
Effects of HBO2 on Elevated Basal Blood Pressure
In 50 treatment sessions where basal SBP was >140 mmHg; SBP was significantly elevated (from 151 ± 11.9 mmHg to 183 ± 26 mmHg, 21%, p <0.001) after HBO2. DBP was significantly increased by 16%. When basal SBP was >170 mmHg (seven sessions), SBP was elevated by 24%, whereas DBP was increased by 21% (p <0.001).
Effects of HBO2 on Low Basal BGL
In 60 sessions where basal BGL was <170 mg/dL (125 ± 21.4 mg/dL), BGL dropped to <100 mg/dL (83.5 ± 11.8 mg/dL, 33%, p <0.001) after HBO2. Where basal BGL was <120 mg/dL in seven sessions (115 ± 21.8 mg/dL), it dropped to <80 mg/dL (67.21 ± 8.7 mg/dL, 41%) after HBO2, p <0.001; two patients developed hypoglycemic symptoms. In 14 treatment sessions, patients had a basal BGL of <100 mg/dL (75 ± 15 mg/dL); after feeding and HBO2 the mean BGL was insignificantly elevated to 95 ± 217.5 mg/dL (p = 0.245).
Effects of HBO2 with Beta Blockers on Blood Pressure and BGL
Beta blockers caused a 19% drop in basal HR in patients with HTN compared to hypertensive patients using other medications, which was increased to 23% after HBO2 (Table 3). After HBO2, a greater reduction in HR was observed in patients using beta blockers compared to patients using other medications (17 vs. 13%). In patients with HTN and DM, HBO2 caused a mean percent (23%) drop in BGL with use of beta blockers, whereas it caused a mean percent (20%) drop in BGL with use of other antihypertensive drugs.
Table 3. Synergistic effects of hyperbaric oxygen and beta blockers on heart rate
Heart rate (beats/min) Type of treatment Number of patients Before HBO2 treatment After HBO2 treatment p value % Beta blocker 9 72.6 ± 9.7 (48−97 beat/min) 60 ± 8 (44−82 beat/min) <0.001 17 No beta blocker 8 89.3 ± 10.1 (60−110 beats/min) 77.9 ± 8.9 (60−101 beats/min) <0.001 13 p value <0.0001 <0.0001 % 19 23 - Full-size table
Side Effects of HBO2 Intervention
One patient with DM who used insulin developed hypoglycemic symptoms during treatment: particularly severe sweating and headache. Her basal BGL was 110 mg/dL, which dropped to 50 mg/dL after HBO2. Another patient developed hypoglycemia during treatment manifested by shivering and sweating. His basal BGL was 150 mg/dL, which dropped to 50 mg/dL after HBO2. One female patient developed an asthmatic attack during therapy and treatment was terminated after 20 min. One patient with HTN developed severe headache, anxiety, and blood pressure was markedly elevated; treatment was terminated after 25 min. One male patient developed ocular complications and was referred for ophthalmological consultation. Two other patients developed ear pain and could not equalize with the increasing pressure; their treatment was terminated during compression phase.
Discussion
The main findings of this study are 1) HBO2 causes a statistically significant elevation in blood pressure and significant drop in HR; 2) blood pressure was higher in patients with DM and HTN compared with hypertensive patients; 3) greater elevations in blood pressure and drops in HR were obtained in patients with HTN and DM compared to other groups; 4) DM causes a greater elevation in blood pressure after HBO2 compared to hypertensive patients, non-hypertensive patients, and non-diabetic patients, 5) patients with HNT and DM showed a greater reduction in HR after HBO2 compared to other groups; 6) the highest reduction in HR was obtained after HBO2 sessions when calcium antagonist was used for the treatment of hypertension; 7) beta blockers significantly decrease HR in hypertensive patients compared to other medications; 8) beta blockers cause a greater elevation in blood pressure and reduction in HR and BGL after HBO2 compared to other medications used for treatment of HTN; 9) a greater elevation of blood pressure after HBO2 was observed in patients whose basal SBP was higher than 140 mmHg; and 10) in DM, hypoglycemia might be encountered after HBO2 when basal BGL was <120 mg/dL.
These observations showed that DM affects HTN control and augments the influence of HBO2 on blood pressure and HR. Coexisting DM and HTN further exaggerate the influence of HBO2 on blood pressure and HR. Similarly, beta blockers increase the effect of HBO2 on blood pressure and HR and to a lesser extent on BGL. Therefore, underlying diseases and types of medical treatment significantly influence the effects of HBO2 on vital signs. It is important for the hyperbaric community to establish new guidelines to determine whether patients with various indications for HBO2 would be eligible for HBO2 based on their diseases, blood pressure, HR or BGL. We believe such an approach will make HBO2 safer than at any other time despite the few complications encountered in practice.
Basically, blood pressure, HR or BGL are influenced by a great number of interventions and factors such as neuronal, hormonal, metabolic, nutritional and psychological and the autoregulatory mechanism. Furthermore, it is not uncommon to find out that many drugs used for treatment of certain illnesses could adversely affect blood pressure, HR or BGL. It is well known that these vital signs are under autonomic nervous system control. Previous studies showed that parasympathetic activity is increased during HBO2, which was ascribed to the increase in the partial pressure of oxygen 21 and 22. Vagal tone is increased during decompression and decreases gradually towards the baseline during decompression (23). Such increases were detected by increased high frequency power of HR variability 21 and 22. Apparently, a healthy heart is characterized by non-homeometric variability, which is elicited by the autonomic nervous system 24 and 25.
Bradycardia, mediated through parasympathetic dominance, has been reported to be a consequence of increased pressure (26). Bradycardia is not influenced by respiratory gases and depth; it is due only to high pressure (6). Normobaric and hyperbaric hyperoxia increase parasympathetic influence in the regulation of the heart (8). Studies showed that using parasympathomimics could ameliorate bradycardia caused by HBO214 and 27.
Vasoconstriction increases blood pressure and activates baroreflex, which may increase parasympathetic activity. Endothelin-1 is increased significantly during HBO2(8). Therefore, endothelin-1-induced vasoconstriction may be involved in this process. As HBO2 increases thromboxane, it may play a role in parasympathetic activation due to vasoconstriction (11). Further, reduced sympathetic activity plays a primary role in the reduction of HR in the hyperbaric environment 28 and 29. Enhanced activity of sympathetic nerves was recognized in the early post-dive period by an elevated plasma epinephrine and norepinephrine (29). However, no statistically significant difference in the changes of mean norepinephrine and dihydroxyphenylglycol levels was observed (8). Therefore, reduction of sympathetic activity during HBO2 and its possible role in bradycardia need further confirmation. Increased sympathetic activity might be expected during an HBO2 session in part due to the patient's anxiety and the intervention. In our patients, vital signs were measured after about 15 min of rest; this interval before the HBO2 session. During the course of treatment, patients will become accustomed to HBO2 over consecutive sessions with a consequent decrease in stress, anxiety or claustrophobia, thus reducing the influences of sympathetic activity that probably increases HR or blood pressure before each treatment session. However, if we presume that elevated HR or blood pressure or even BGL before the sessions was due to sympathetic stimulation as a result of claustrophobia or because the patient had just had his/her dressing changed or was anxious, the effect of the sympathetic stimulation will continue while the patient is in the chamber and increasing HR or BGL further.
Studies in healthy volunteers showed that HBO2 reduced left ventricular pre-load, increased left ventricular after-load, and decreased left ventricular systolic performance (9). In rats, HBO2 decreased cardiac output, cardiac work, and left ventricular performance indices without a change in pre-load or after-load (16). Oxygen exposure notably stimulated the myocardium by elevating the left ventricular pressure, elevated systolic arterial pressure and pulse pressure, and induced bradycardia in conscious rats 13 and 30. A reduction in cardiac output and left ventricular systolic performance is not consistent with elevated blood pressure observed after HBO2.
HBO2 significantly decreased cortisol levels (8). Both suppressed ADH secretion and stimulated atrial natriuretic peptide secretion caused hyperbaric diuresis (31). HBO2 normalized the plasma renin level and reduced aldosterone concentration in patients with chronic heart failure (32). Consequently, the mechanism of elevated blood pressure after HBO2 is not clear. Vasoconstriction might play a role in the mechanism of action, but other factors might also be involved.
Actually, we have two important issues: one is bradycardia and the other is elevated blood pressure. In the autonomic nervous system, stimulation of alpha 1 causes vasoconstriction and stimulation of beta 1 causes tachycardia. HBO2, due either to hyperoxia or high pressure, might stimulate α1 receptors and downregulate β1 and β2 receptors. β1 stimulates the heart and β2 relaxes the smooth muscles of the bronchia and blood vessels. Findings support that HBO2 increases airway resistance and decreases respiratory volume (17). Furthermore, our study showed that beta blockers, which inhibit β1 and β2, exaggerate both HBO2-induced bradycardia and HBO2-induced elevation of blood pressure.
Therefore, our recommendation is to avoid using beta blockers in patients who are scheduled for HBO2. Similarly, Ca2+ channel blockers with anti-arrhythmic effects must be used with care in patients undergoing HBO2. With use of calcium blockers, the greatest reduction in HR was observed after HBO2. Calcium blockers cause reflex tachycardia, which is inhibited by beta blockers (33). This effect is similar to the effect of HBO2. Angiotensinogen-converting inhibitors might be the alternative. Ang-11 receptor blockade inhibits hyperbarically induced left ventricular hypertrophy and prevents previously shown changes in cardiac function and morphology, as well as myocardial mass, after 40 consecutive exposures to HBO2(34).
