Lecture of Oral & Maxillofacial Surgery, Faculty of Dental Medicine, Al Azhar University ... Background: Hyperbaric Oxygen Therapy (HBOT) is increasingly being ...
Hyperbaric Oxygen as an adjunctive therapy in Maxillofacial Infection in Diabetic Patients Mohammed Abd El-Akher*, Ayman Hegab** * Lecture of Oral & Maxillofacial Surgery, Faculty of Dental Medicine, Al Azhar University in Cairo. ** Lecture of Oral & Maxillofacial Surgery, Faculty of Dental Medicine, Al Azhar University in Cairo.
Abstract Background: Hyperbaric Oxygen Therapy (HBOT) is increasingly being accepted as a beneficial adjunct to diverse clinical conditions. Non-healing ulcers, chronic wounds and refractory osteomyelitis are a few conditions for which HBOT has been extensively tried out. The aim of this study was to evaluate the effectiveness of HBOT as an adjunctive method in management of maxillofacial infection of the diabetic patients. Patients and Methods: In this study, 6 diabetic patients with age range from 40 to 65 years presented to the maxillofacial clinic with sever maxillofacial infection were included in this study. Two patients suffered from facial cellulites and 4 patients suffered from submandibular and masticatory space infection with trismus. Treatment started with empirical antibiotic and the patients were submitted to HBOT for 10 sessions immediate after culture sampling and incision and drainage (I&D). Results: All the patients in this study showed rapid significant improvement of the infection within few days without serious complications. Complete resolution of the infection was observed after finishing the sessions of HBOT Conclusions: Because infections in elderly patients with DM can be severe and life threatening, clinicians must be cognizant of atypical manifestations of illness and maintain a high index of suspicion for various infectious processes common to this population. Prompt recognition and treatment of such infections with broad-spectrum antimicrobial agents and HBOT as adjunctive method are critical to lower morbidity and mortality in this vulnerable population.
.
1
Review of literature: The negative effects of diabetes mellitus on the immune system have been extensively investigated. These effects impact greatly on the host’s ability to prevent the establishment of, and bring resolution to a variety of head and neck infections. The main etiologic factor in diabetes mellitus that leads to dysfunction in the immune system is hyperglycemia. All the major cell types involved in the immune defense are affected. Cellular elements of the innate immune system, including neutrophils and monocytes/macrophages, have altered function. In the neutrophils, functions such as adherence, chemotaxis, and phagocytosis may be down- regulated. This results in a less effective defense against a microbial challenge. The neutrophils from diabetic patients also produce less free oxygen radicals, which reduce their ability to make toxic metabolites for release against microbes. Monocytes and macrophages may have up-regulated catabolism of pro-inflammatory cytokines as well as increased production of matrix metalloproteases, such as collagenase. This creates an imbalance that is detrimental to the containment of head and neck infections. The hyperglycemic state may also lead to a decrease in fibroblast proliferation and synthesis of collagen, impairing tissue turnover and wound repair. (1-3) It has been proposed that the formation of advanced glycation end-products (AGEPs), which form as a result of glucose irreversibly binding to proteins and lipids in the face of prolonged hyperglycemia, is a key event in the generation of the defects seen in diabetes. Glycation endproducts can bind to receptors on various cells, such as leukocytes, and affect their function. The up regulation of tissue destructive cytokines produced by the monocytes and macrophages may be a result of AGEP binding. AGEPs also alter the solubility of collagen and may play a role in the changes seen in small and large blood vessels. This collagen interaction may result in the accumulation of AGEPs on the basement membrane, affecting the exchange of nutrition, neutrophil migration, and the diffusion of antibodies and oxygen. As a group, these effects should have a detrimental effect on the wound healing apparatus and can lead to serious and life-threatening infections in patients with DM. Prompt recognition of infection and treatment with appropriate empirical broad-spectrum antimicrobial agents, in conjunction with surgical intervention, is often necessary to eradicate such infections. (4-6) Shallow oxygen gradient and diabetic tissue: The fundamental flaw of a shallow oxygen gradient in the diabetic tissue is shared by the radiated tissue, which is another tissue fraught with wound healing complications and tissue non viability. In each of these tissues the shallow oxygen gradient
2
(less than 20 mmHg) fails to generate macrophage chemotaxis and fail to stimulate macrophage secretion of angiogenic factors and fibroblast growth factors. Shallow oxygen gradient predisposes wounds to infection, because the neutrophil-mediated killing of bacteria by free radicals is decreased. Hyperbaric oxygen develop oxygen gradient range from 50-250 mmHg which restores the defense against infection by neutrophil-mediated free radicals, increases the rate of killing of some common bacteria by phagocytes and increase the macrophage chemotaxis and secretion of angiogenic and fibroblast growth factors. In addition, hyperbaric oxygen alone is bactericidal for certain anaerobes. (7, 8) Role of Hyperbaric oxygen therapy: HBOT is defined as breathing 100% oxygen while in an enclosed system that is pressurized to greater than one atmosphere (sea level). The pressure is usually about 2.4 absolute atmospheres for about 90 minutes. HBOT does not work by saturated more hemoglobin than can already exist at room-air sea level breathing. Instead, it elevate the Pao2 from the normal 80-100 mmHg range to as much as 1000-1200 mmHg and the volume percent of oxygen in the blood from less than 1% to about 6% by dissolving much more oxygen in the blood and interstitial fluids.(9) Physiologic Benefits of HBOT Improves leukocyte function and bacterial killing, Antibiotic potentiation, Enhances collagen synthesis and cross linking, Improves cellular metabolism and host immune response, Direct toxic affect to anaerobic bacteria, Inactivates clostridium toxin, The neutrophils-mediated killing of bacteria by free radicals, Stimulate macrophage secretion of angiogenic factors and fibroblast growth factors, Increase the macrophage chemotaxis and Adequate tissue oxygen tension also facilitates fibroblast proliferation and new capillary formation. Adequate tissue oxygen tension also facilitates fibroblast proliferation, new capillary formation.(9, 10) Contraindications, Risk Factors and Side Effects: Once a person is recognized as a candidate for HBOT, a history and physical must be obtained to determine if there are any contraindications to therapy which include the following: Untreated pneumothorax, Prior chemotherapy treatment with Adriamycin or Bleomycin, current treatment with Cis-platinum, or Antabuse, Early model pacemakers not designed to tolerate pressure, Optic neuritis because exacerbation of retinal inflammation and hyperemia is feared and Immunosuppressive disorders because of risk of development of viral encephalitis.(10 , 11) Relative Contraindications Include:
3
Chronic sinusitis – patients need to be able to “clear their ears” during the dive, which feels similar to ears popping during an airplane descent. If there is an accumulation of fluid in the ear, treatment may need to be delayed. Alternatively myringotomy tubes may be used to alleviate this issue. Seizure disorder, Severe Chronic Obstructive Pulmonary Disease or emphysema, High fever may lead to seizure. No diving if temperature is greater than 100°F and History of spontaneous pneumothorax. (10, 11) Side Effects:Ear barotraumas – the most common complication of HBOT. This can frequently be avoided with proper patient education. Sinus squeeze – discomfort felt in the sinuses with pressurization, Temporary myopia – with multiple treatments patients may notice some difficulty with distant vision while enjoying the temporary ability to read without glasses. This resolves within two months after completing HBOT. Dental pain – air space left under a filling, Claustrophobia – with newer larger chambers this is less than 10 % and can be alleviated with benzodiazepines before treatment and Seizures – very rare from oxygen toxicity .(10 , 11)
Patients and Methods In this study, 6 diabetic patients with age range from 40 to 65 years presented to the maxillofacial clinic with sever maxillofacial infection were included in the study. Two patients suffered from facial cellulites and 4 patients suffered from submandibular and masticatory space infection with trismus. Sample and antibiotic sensitivity test was done first followed by administration of empirical antibiotic therapy.
Most patients are given IV antibiotics targeting gram positive cocci and
anaerobes. They also should receive antibiotics that cover gram negative aerobes as well. Common regimens include Unasyn (Ampicillin / Sulbactam), Clindamycin or second generation cephalosporins. Incision and drainage (I& D) was done under general anesthesia followed the administration of the empirical antibiotic and adjustment of the blood sugar level with insulin. Once culture results can be obtained, antibiotic therapy can be tailored to the organism in question. Once the patient is able to tolerate oral antibiotics then they are switched over. The patients were submitted to HBOT for 10 sessions immediate after culture sampling and I&D.
Results All the patients in this study showed rapid significant improvement of the infection within few days in term of improvement of the facial swelling and increase in the mouth opening with complete resolution of the trismus. Complete resolution of the infection was observed after finishing the sessions of HBOT. Patients showed complete resolution before finishing the sessions of HBOT
4
instructed to complete the sessions to prevent the failure of therapy. Patients were held in the antibiotic therapy during the treatment period.
Discussion: The elevated serum glucose levels associated with diabetes mellitus (DM) alter host immune responses, resulting in a well documented increase in the predisposition to infectious processes. Furthermore, the cumulative effect of age-related immune senescence, superimposed on this enhanced risk of infections, can lead to serious and life-threatening infections in elderly patients with DM. Diabetes mellitus can have a significant impact on the delivery of dental care. It is important for dentists to be familiar with the medical management of patients with DM, and to recognize the signs and symptoms of undiagnosed or poorly controlled disease.(2-3) Hyperbaric oxygen has been described as “a therapy in search of diseases.” Many of its past uses had little or no scientific support. The discovery of beneficial cellular and biochemical effects has strengthened the rationale for administering hyperbaric oxygen as primary therapy in patients with severe carbon monoxide poisoning, decompression sickness, and arterial gas embolism, and as adjunctive therapy for the prevention and treatment of Osteoradionecrosis, clostridial myonecrosis, infection in diabetes patients (diabetic foot) and compromised skin grafts and flaps.(10-11) The results of this study suggest that HBO may be beneficial as an adjunctive treatment for maxillofacial infection of the diabetic patients. Physicians are encouraged to consider HBOT for appropriate patients. In some cases this may be a life saving treatment, and in many other situations serious complications such as cavernous sinus thrombosis can most definitely be avoided. HBOT is generally safe and well-tolerated.
Conclusions: Because infections in elderly patients with DM can be severe and life threatening, clinicians must be cognizant of atypical manifestations of illness and maintain a high index of suspicion for various infectious processes common to this population. Prompt recognition and treatment of such infections with broad-spectrum antimicrobial agents and HBOT as adjunctive method are critical to lower morbidity and mortality in this vulnerable population.
5
References 1- Calvet CM, Yoshikawa TT. Infections in diabetics. Infect Dis Clin North Am 2001; 15:407–21. 2- Harris MI, Hadden WC, Knowler WC, et al. Prevalence of diabetes and impaired glucose tolerance and plasma glucose levels in US population aged 20–74 years. Diabetes 1987; 36:523–34. 3-Geerlings S, Hoepelman A. Immune dysfunction in patients with diabetes mellitus (DM). FEMS Immunol Med Microbiol 1999; 26:259–65. 4-Gallacher S, Thomson G, Fraser WD, Fisher BM, Gemmell CG, MacCuish AC. Neutrophil bactericidal function in diabetes mellitus: evidence for association with blood glucose control. Diabet Med 1995; 12:916–20. 5-Delamaire M, Maugendre D, Moreno M, Le Goff MC, Allannic H, Genetet B. Impaired leukocyte function in diabetic patients. Diabetic Med 1997; 14:29–34. 6-Tierney MR, Baker AS. Infections of the head and neck in diabetes mellitus. Infect Dis Clin North Am 1995; 9:195–216. 7-Knighton DR, Silver IA and Hunt TK: regulation of wound healing angiogenesis: effect of oxygen gradients and inspired oxygen concentration. Surgery, 1981: 90: 262-269 8-Ross R, Raines EW, Brown-Pope DF: The biology of platelets derived growth factor, Cell, 1986, 46:155-169 9- Marx, RE, Osteoradionecrosis: A New Concept in Path physiology. J Oral Maxillofacial Surgery 1983: 41 ;( 5):283-288. 10- Kindwall, EP. A History of Hyperbaric Medicine In: Hyperbaric Medicine Practice, 2nd Ed, Kindwall EP, editor, Flagstaff (AZ): Best Publishing Company; 1999. p. 1-20. 11- Sheffield, PJ, Desautels, DA. Hyperbaric and hypobaric chamber fires: a 73-year analysis. Undersea Hyper Med 1997;24(3):153-164.
6