J. Maxillofac. Oral Surg. DOI 10.1007/s12663-013-0611-7
REVIEW PAPER
Fever After Maxillofacial Surgery: A Critical Review Amelia Christabel • Ravi Sharma • R. Manikandhan P. Anantanarayanan • N. Elavazhagan • Pramod Subash
•
Received: 17 September 2013 / Accepted: 28 December 2013 Ó Association of Oral and Maxillofacial Surgeons of India 2014
Abstract Purpose The aim of this paper is to review the pathophysiology of thermoregulation mechanism, various causes of fever after maxillofacial surgery and the different treatment protocols advised in the literature. Discussion Fever is one of the most common complaints after major surgery and is also considered to be an important clinical sign which indicates developing pathology that may go unnoticed by the clinician during post operative period. Several factors are responsible for fever after the maxillofacial surgery, inflammation and infection being the commonest. However, other rare causes such as drug allergy, dehydration, malignancy and endocrinological disorders, etc. should be ruled out prior to any definite diagnosis and initiate the treatment. Proper history and clinical examination is an essential tool to predict the causative factors for fever. Common cooling methods like tepid sponging are usually effective alone or in conjunction with analgesics to reduce the temperature. Conclusion Fever is a common postoperative complaint and should not be underestimated as it may indicate a more serious underlying pathology. A specific guideline towards the management of such patients is necessary in every A. Christabel R. Sharma R. Manikandhan P. Anantanarayanan N. Elavazhagan Department of Oral and Maxillofacial Surgery, Meenakshi Ammal Dental College and Hospital, Maduravoyal, Chennai 600 095, Tamil Nadu, India R. Sharma (&) Nandan Apartment, C-72, Sarojini Marg, C-Scheme, Jaipur 302001, Rajasthan, India e-mail: [email protected] P. Subash Renai Medicity, Kochi, Kerala, India
hospital setting to ensure optimal care towards the patients during post operative period. Keywords Drug fever Maxillofacial infection Maxillofacial surgery Postoperative fever Pyrogen
Introduction Postoperative pain and fever are among the most common complaints after maxillofacial surgery. Despite being the most frequently encountered clinical sign, there is general dilemma among medical and nursing staff about the various terminologies used for the rise in body temperature. Fever is defined as an elevation of body temperature that exceeds the normal daily variation and occurs in conjunction with an increase in the hypothalamic set point. A fever of [41.5 °C ([106.7 °F) is called hyperpyrexia. Unlike fever, hyperthermia is characterized by an uncontrolled increase in body temperature that exceeds the body’s ability to lose heat without any change in hypothalamic set point. Core body temperature of higher than 101.5° Fahrenheit or 38.5° Celsius develops when exogenous or endogenous pyrogens stimulate the hypothalamus to develop a higher than normal thermal set point [1]. Exogenous pyrogens originate from outside the body and include microbes and their various toxins and products. Endogenous pyrogens are derived internally, and include various febrile mediators like cytokines and prostaglandins [2]. Exogenous pyrogens typically stimulate the production of endogenous pyrogens. However, certain endogenous molecules such as complement, bile acids, lymphocyte derived molecules and various antigen-antibody complexes may also induce the production of endogenous pyrogens [3].
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Fever is for the most part beneficial to the patient and clinician as it alerts one to the disease process and it must be qualified and verified in accordance to the etiology and the symptoms in order to institute prompt treatment [4]. Fever has also been postulated to be protective against allergic sensitisation and atopic asthma in children [5, 6]. In the field of surgery, especially during the postoperative period, fever is beneficial as a predictive tool to detect the onset of any complications [7]. Also, it is a sign that the host is putting up a defence against the onset of infection [8]. However excessive fever causes severe stress to the patient which may hamper postoperative recovery [9]. This review article discusses the pathophysiology, etiology and treatment approach for post operative fever after maxillofacial surgery.
Table 1 Causes of fever Infective
Surgical site infection, urinary tract infection (UTI), pneumonia, foreign body [graft/implant] infection, septicaemia, sinusitis, otitis media, catheter associated infection, meningitis, bacterial endocarditis, osteomyelitis, opportunistic infection/hospital acquired infection (HAI) in immunocompromised patients or due to antibiotics
Inflammatory
Inflammation, surgical trauma, allergic reaction, graft rejection, transfusion reaction, hematoma, pancreatitis, atelectasis
Thrombosis
Deep vein thrombosis, pulmonary embolism
Vascular
Cerebral infarction, subarachnoid hemorrhage, myocardial infarction, surgical site ischemia, flap necrosis, bowel ischemia or infarction
Drugs
Drug induced fever, malignant hyperthermia, alcohol or drug (baclofen, steroid) withdrawal syndrome
Miscellaneous
Dehydration, neoplastic fever, hyperthyroidism, hypoadrenalism
Pathophysiology of Fever The general manifestations of a febrile response includes shivering, chills, loss of appetite, malaise, anorexia, decreased secretions, absence of sweating, and an increase in blood pressure as well as heart rate [10]. Thermoregulation is a dynamic process consisting of three components. Thermosensors located at peripheral nerve endings as well as the central hypothalamus are responsible for detecting both increase and decrease in temperature. The second component consists of reflex mechanisms to control temperature; namely heat dissipating and heat generating body systems. The third component is a neuronal coronal network of neurons within the hypothalamus. These act as negative feedback response systems [11]. As discussed earlier, postoperative fever is produced by various endogenous and exogenous pyrogens which are brought about by a myriad of causes as summarized in Table 1. The final reaction is brought about by stimulation of the hypothalamus, or more specifically at the organum vasculosum of the laminae terminalis. This area synthesizes prostaglandin E2 in response to these pyrogens, and this in turn releases cyclic adenosine monophosphate. This acts as a neurotransmitter which results in fever [12]. Fever is essentially a sequence of negative feedback, in which phases of chill, fever and flush occur depending on the stimulation of various mechanisms [13].
Etiology of Postoperative Fever Postoperative fever is a common event in patients who undergo major surgery. The incidence may range from 10 to 40 % [14], and maybe due to both infectious and noninfectious causes. More commonly postoperative fever is a
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benign event, with only a small percentage being due to an infection. The literature describes a mnemonic for remembering the causes of postoperative fever, the ‘5W’Wind, Water, Wound, Weins/Wings and Wonder drugs [15]. Ansari [16] divided the occurrence of postoperative infection into several time periods as immediate (within 24 h), acute (24–72 h), subacute or delayed (within 1st week). Jadwani et al. [17] also included intraoperative fever into this classification. The different causes of postoperative fever to be suspected during these time periods have been summarised in Table 2. The most common causes of post operative fever have been described in detail as follows.
Inflammatory Causes Inflammation is the normal human body response to any form of damage to cells. The mediators of any inflammatory response include the various cytokines like prostaglandins and leukotrienes. Miyawaki et al. [9] concluded that following maxillofacial surgery, there is an elevation in the levels of various cytokines, most notably interleukin 6 (IL-6). The elevation of plasma IL-6 correlates significantly with a rise in core body temperature following major surgical procedure, however, plasma interleukin 3 and tumour necrosis factor alpha did not significantly correlate with change in temperature. The incidence of post operative fever due to inflammatory causes largely depends upon the duration of the surgery, intraoperative transfusion, pre-existing infection and preoperative antibiotics [10]. Fever developing in patients who underwent organ transplant, grafting or
J. Maxillofac. Oral Surg. Table 2 Classification based upon time of onset and probable causes for fever Etiology
Infection
Time of onset Intra-operative
Immediate (within 24 h)
Acute (24–72 h)
Subacute or delayed (\1 week)
Preoperative infection
Clostridium perfringens or streptococcal group A infection
Surgical site infection, aspiration pneumonia, UTI, catheter associated infections, otitis media
Surgical site infection, UTI, infected prosthesis or graft, subacute bacterial endocarditis
Surgical trauma, transfusion reaction, subarachnoid haemorrhage
Atelectasis, graft rejection, allergy, pancreatitis
Graft rejection
Inflammation
Drugs
Anesthetic agents
Drug reaction, malignant hyperthermia
Drug fever
Drug or alcohol withdrawal
Vascular
Myocardial infarction, organ infarct
Fat embolism, myocardial infarction
DVT
DVT, pulmonary embolism, cavernous sinus thrombosis
Others
Heat insulation
hyperthyroidism
Hypoadrenalism, dehydration
Dehydration
reconstruction procedure is suggestive of graft rejection or infection [18]. Infection Infection is a common cause of postoperative fever. Although the majority of postoperative fever is benign in nature and more of an inflammatory response, an infectious etiology cannot be ruled out, especially in prolonged fever episodes. Most authors consider that extensive workups on patients with postoperative fever in search of an infectious etiology are a waste of resources [14, 19]. Various toxins produced by microorganisms act as exogenous pyrogens which cause rise in body temperature. Enterotoxins produced by staphylococcus aureus and superantigens by streptococcal species are common examples of pyrogenic toxins [20]. Nosocomial infections or hospital acquired infections (HAI) are to be dreaded in the postoperative setting, due to their virulence and resistance to antibiotics. Common pathogens isolated in the affected patients in several studies are coagulase-negative staphylococci, Staphylococcus aureus, Enterococcus species, Candida species, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter species, Acinetobacter baumannii, Klebsiella oxytoca and other multidrug resistant microorganisms such as methicillin resistant staphylococcus aureus [21–23].
Table 3 Drugs causing fever Common agents
Rare agents
Antibiotics Amphotericin B
Cimetidine
Anti tubercular drugs
Antitubercular drugs
Cephalosporins
Vancomycin
Penicillin
Nitrofurantoin
Sulfonamides
Tetracyclins
Anesthetic agents and analgesics Barbiturates
Cocaine
Procainamide
Halothane (general anesthetic)
Salicylates
Non steroidal anti inflammatory drugs (NSAIDS)
Chemotherapeutic agents Asparginase
Hydroxyurea
Bleomycin Cardiovascular drugs Methyldopa
Streptokinase
Quinidine sulphate
Hydralazine
Others Antihistamines
Allopurinol
Phenytoin
Azathioprine Diuretics Heparin Propylthiouracil Succinylcholine Baclofen and steroids (withdrawl symptom)
Dehydration Fever due to dehydration and vice versa is a phenomenon seen more often in neonates and infants [24–26]. Dehydration is a common problem seen in patients who underwent maxillofacial surgery due to inadequate intraoperative
and perioperative fluid management, diarrhoea and vomiting, difficulty in oral intake and patient noncompliance. Dry mouth and skin, decreased urine output, thirst, cardiovascular and neurological changes are indicative of dehydration fever in post-operative patients [27].
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Drugs
Fever Specific to Oral and Maxillofacial Surgery
Adverse and unwanted drug reactions may result in fever, especially in the immediate postoperative period. Fever may also be the presenting symptom of drug allergy [28]. Drug induced fever or ‘‘drug fever’’ is also seen accompanying the administration of certain drugs, most notably beta lactam antibiotics. Based upon the literature review and frequency of drug used during post operative period Table 3 provides a summary of drugs that may cause fever following their use [16, 17, 29–37]. Another drug induced reaction which is although rare but life threatening, associated with general anesthetic agents and/or succinylcholine is known as malignant hyperthermia (MH). MH is predominantly seen with administration of succinylcholine (77 % cases), halothane [60 %] and other general anesthetic agents with the incidence rate of approximately 1:15,000 among children and 1:50,000 in adults [38]. MH presents with an autosomal dominant inheritance pattern and predilection for males. MH is considered to be abnormal distribution of myoplasmic calcium (Ca2?). Clinical features include tachycardia, high fever, tachypnea, cardiac dysrhythmia, muscle rigidity (most frequently in masseter muscle producing trismus), cyanosis and death in severe and unattended cases [39, 40]. Drug-induced fever may also be the result of a delayed hypersensitivity reaction (type IV) and its characteristics resemble those of an allergic reaction. The onset of fever is usually after 7–10 days of drug administration, high variations, disappears soon after discontinuation of the culprit drug and recurs when drug is given to the patient again [30, 31].
Surgical procedures of maxillofacial region pose similar challenge to the immune response of the body and other factors already discussed in this article. There is no data suggesting any significant risk of post operative fever after maxillofacial procedure as compared to the surgeries of other parts of the body, however, few studies have highlighted some distinct etiopathogenesis in dental and maxillofacial surgery. Use of compressed air and air rotor handpiece in third molar extractions has shown significant risk of mediastinitis and subcutaneous emphysema where fever can be one of the presenting symptoms [44–46]. Infective endocarditis is another serious complication following minor or major surgical procedures in post operative period which should be ruled out based upon the medical history and cardiovascular examination [47]. Fever in the intraoperative period can be seen in patients with preoperative fever due to severe infections like Ludwig’s angina or extensive space infections surrounding a non reduced fracture which may also induce bacteremia on manipulation during surgery [48]. Another rare but life threatening complication is toxic shock syndrome (TSS) resulting from Staphylococcus aureus infection where fever is a common presenting symptom. TSS has been reported following nasal surgery, sinus surgery and other facial cosmetic procedures with strong association between nasal packs and splints and risk of TSS [49–52]. Low grade fever (approximately 38 °C) is a common finding after orthognathic surgery which usually subsides in first 48 h [53]. Gordon et al. [54] have shown that the severity of mandibular fractures and patient general health status correlates with the postoperative inflammatory complications. Bone grafts, mini plates and screws can produce inflammatory response or may become infected. Any patient presenting with localized symptoms and/or fever should be suspected for possible graft infection or allergic reaction and appropriate radiographic and microbiological tests should be carried out. Post operative fever is also associated with donor site morbidity [55]. Certain procedures like rib graft harvesting [56] and anterior iliac bone harvesting [57] are commonly used as adjuncts to various maxillofacial procedures and now use indwelling catheters for local post operative analgesia. Skin around the catheter site should be dressed every day and the catheter should be removed within 48 h, as their prolonged use could lead to infection and thereby fever. Maintaining the oral wound is a great challenge to the surgeon and for the patient as the mucosa is mobile and fragile, oral cavity harbours large microflora (both pathognomic and non-pathognomic), unsatisfactory
Other Causes Other causes of fever during post-operative period include malignancy arising due to cytokines (tumour necrosis factor TNF, interleukins 1 and 6 and interferon IFN) produced either by host macrophages in response to tumour, or sometimes by the tumour itself. The cytokines act on hypothalamus similar to prostaglandins causing elevation in the thermostatic set point [41]. Endocrine conditions such as hyperthyroidism or thyroid storm, hypoadrenalism may produce fever. Rise in core temperature can be indicative of deep vein thrombosis (DVT), pulmonary embolism, myocardial infarction and bowel ischemia are other possible serious complications during post-operative period. Atelectasis is considered to be an etiological factor by some authors [16, 17] however, other studies contradicts any correlation between post operative fever and developing atelectasis [42, 43].
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dressing techniques and regular contamination of the wound with saliva, water and food. Systemic antibiotic prophylaxis, preoperative local antiseptics and perioperative irrigation techniques have proved to be successful in reducing risk of surgical site infection [58–60]. A good anti microbial mouthwash has to be a mandate in all surgical procedures carried out intraorally [61]. Even in patients who have local, regional or free flaps and subjected to a nasogastric feeding tube, it is vital to maintain the oral hygiene so as to prevent infection and wound breakdown intraorally. Significant incidence of fever after palatoplasty has been reported. The author noted that the hydration was an important factor in development of post operative fever. Non weaned patients had larger fever volume as compared to weaned patients in first 48 h suggesting the importance of oral feed [62]. Similarly, another study reveals strong correlation of post operative temperature with the age of the patient of less the 24 months [63]. These findings strongly indicate that hydration and nutritional support is the major challenge in maxillofacial patients due to intraoral wound and inability to eat. Several scientific literatures have been published regarding incidence of malignant hyperthermia in dentomaxillofacial procedures, including lethal ones. With the advent of dantrolene sodium in the management of the MH, the mortality has been reduced from 80 to 10 % [64–68].
Consequences and Complications of Post-Operative Fever Fever causes rise in basal metabolic rate, increased oxygen demand, increased heart rate. As already discussed, high temperature may also induce dehydration in children. Associated symptoms such as chills, rigors, malaise can be quiet distressing to the operated patient. It is considered that for every rise of 1 °C above 37 °C, there is approximately 13 % increase in oxygen consumption. High fever can aggravate pre-existing cardiac, cerebrovascular, or pulmonary insufficiency and can induce mental changes in patients with organic brain disease. Children with a history of febrile or non febrile seizure should be treated immediately to reduce fever although it is unclear what triggers the febrile seizure and no correlation has been established between absolute temperature elevation and onset of a febrile seizure in susceptible children [1].
Management Core body temperature higher than 40° C is considered to be harmful and demand active intervention [69].
Lesperance et al. [14] conducted a prospective observational study of 1,032 postsurgical patients to determine the incidence and utility of extensive postoperative fever evaluations. 23.7 % of their patients experienced postoperative fever, out of which in 18 patients it was due to a postoperative infection. However the authors claim that 50 % of the diagnosis could have been made solely by clinical examination. They came to a conclusion that postoperative fever is common and evaluation should be focussed on clinical examination and no laboratory investigations are necessary in low risk patients within 72 h of surgery. Other studies confirm that routine blood cultures are also unnecessary in the early postoperative fever patient [11, 70, 71]. Laboratory and imaging studies should therefore only be used if necessary, depending on the history and physical examination. Blood cultures should be reserved for patients with pre-existing medical comorbidities or at an increased risk for infection. It is the point to emphasize that the proper history and thorough clinical examination should suffice to elicit the cause of fever and to decide whether treatment is indicated in the presenting situation. Treatment of postoperative fever includes cooling down procedures, various drugs to control body temperature, and specific treatment of the cause. It is necessary to arrive at a definitive diagnosis before beginning any form of therapy, however, fever up to 72 h are to be expected. Common physical cooling methods include sponging and bed fans; while more radical methods include sponging with alcohol, hypothermic mattresses or ice packs [17]. Methods like intraperitoneal lavage of cool fluid, gastric lavage or enemas with iced water and extraperitoneal circulation should be reserved for emergency situations. Monitoring of body temperature is, of course, necessary to avoid overzealous cooling [13]. Non-steroidal anti-inflammatory drugs (NSAID) include aspirin and its congeners act by inhibiting the synthesis of prostaglandins via the cyclooxygenase pathway. They are the most widely used drugs to control fever. Several studies state superiority of one NSAID over others or comparative efficiency of various combinations of these agents. Ibuprofen and paracetamol (acetaminophen) have been widely used and are considered to be safe and effective in febrile patients [72–75]. Fever due to infectious cause may require modification in antibiotic therapy depending on the culture and sensitivity examination. Surgical site infection can be prevented as well as controlled by antimicrobial dressings and irrigation with povidone iodine or chlorhexidine, however, few cases may warrant re-exploration and surgical debridement while, necrotic or infected graft should be removed. HAI and multidrug resistant microorganisms should be treated aggressively with appropriate
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antimicrobials such as cephalosporins, aminoglycoside or carbapenem [76, 77]. Other more specific causes require more specific approach in conjunction with antipyretic therapy, for instance, corticosteroids and antihistamine for allergic drug reactions [78], dantrolene sodium in malignant hyperthermia [65–67], antiepileptic drugs and benzodiazepines in epilepsy with febrile seizures [79] and anticoagulant prophylaxis for deep vein thrombosis [80]. In depth discussions of such conditions are however, beyond the scope of this article.
Conclusion In conclusion, fever in the postoperative patients is a common benign occurrence in any form of surgery, including maxillofacial surgery. However, an occurrence of fever should not be underestimated as it may indicate a more sinister underlying pathology. A specific guideline towards the management of such patients is necessary in every clinical setting to ensure optimal care towards the patients that entrust their health and well-being into the surgeon’s hands. Acknowledgments The authors affirm that they have no financial affiliation (e.g., employment, direct payment, stock holdings, retainers, consultantships, patent licensing arrangements or honoraria), or involvement with any commercial organization with direct financial interest in the subject or materials discussed in this manuscript, nor have any such arrangements existed in the past 3 years. Conflict of interest
The authors deny any conflict of interest.
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REVIEW PAPER
Fever After Maxillofacial Surgery: A Critical Review Amelia Christabel • Ravi Sharma • R. Manikandhan P. Anantanarayanan • N. Elavazhagan • Pramod Subash
•
Received: 17 September 2013 / Accepted: 28 December 2013 Ó Association of Oral and Maxillofacial Surgeons of India 2014
Abstract Purpose The aim of this paper is to review the pathophysiology of thermoregulation mechanism, various causes of fever after maxillofacial surgery and the different treatment protocols advised in the literature. Discussion Fever is one of the most common complaints after major surgery and is also considered to be an important clinical sign which indicates developing pathology that may go unnoticed by the clinician during post operative period. Several factors are responsible for fever after the maxillofacial surgery, inflammation and infection being the commonest. However, other rare causes such as drug allergy, dehydration, malignancy and endocrinological disorders, etc. should be ruled out prior to any definite diagnosis and initiate the treatment. Proper history and clinical examination is an essential tool to predict the causative factors for fever. Common cooling methods like tepid sponging are usually effective alone or in conjunction with analgesics to reduce the temperature. Conclusion Fever is a common postoperative complaint and should not be underestimated as it may indicate a more serious underlying pathology. A specific guideline towards the management of such patients is necessary in every A. Christabel R. Sharma R. Manikandhan P. Anantanarayanan N. Elavazhagan Department of Oral and Maxillofacial Surgery, Meenakshi Ammal Dental College and Hospital, Maduravoyal, Chennai 600 095, Tamil Nadu, India R. Sharma (&) Nandan Apartment, C-72, Sarojini Marg, C-Scheme, Jaipur 302001, Rajasthan, India e-mail: [email protected] P. Subash Renai Medicity, Kochi, Kerala, India
hospital setting to ensure optimal care towards the patients during post operative period. Keywords Drug fever Maxillofacial infection Maxillofacial surgery Postoperative fever Pyrogen
Introduction Postoperative pain and fever are among the most common complaints after maxillofacial surgery. Despite being the most frequently encountered clinical sign, there is general dilemma among medical and nursing staff about the various terminologies used for the rise in body temperature. Fever is defined as an elevation of body temperature that exceeds the normal daily variation and occurs in conjunction with an increase in the hypothalamic set point. A fever of [41.5 °C ([106.7 °F) is called hyperpyrexia. Unlike fever, hyperthermia is characterized by an uncontrolled increase in body temperature that exceeds the body’s ability to lose heat without any change in hypothalamic set point. Core body temperature of higher than 101.5° Fahrenheit or 38.5° Celsius develops when exogenous or endogenous pyrogens stimulate the hypothalamus to develop a higher than normal thermal set point [1]. Exogenous pyrogens originate from outside the body and include microbes and their various toxins and products. Endogenous pyrogens are derived internally, and include various febrile mediators like cytokines and prostaglandins [2]. Exogenous pyrogens typically stimulate the production of endogenous pyrogens. However, certain endogenous molecules such as complement, bile acids, lymphocyte derived molecules and various antigen-antibody complexes may also induce the production of endogenous pyrogens [3].
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Fever is for the most part beneficial to the patient and clinician as it alerts one to the disease process and it must be qualified and verified in accordance to the etiology and the symptoms in order to institute prompt treatment [4]. Fever has also been postulated to be protective against allergic sensitisation and atopic asthma in children [5, 6]. In the field of surgery, especially during the postoperative period, fever is beneficial as a predictive tool to detect the onset of any complications [7]. Also, it is a sign that the host is putting up a defence against the onset of infection [8]. However excessive fever causes severe stress to the patient which may hamper postoperative recovery [9]. This review article discusses the pathophysiology, etiology and treatment approach for post operative fever after maxillofacial surgery.
Table 1 Causes of fever Infective
Surgical site infection, urinary tract infection (UTI), pneumonia, foreign body [graft/implant] infection, septicaemia, sinusitis, otitis media, catheter associated infection, meningitis, bacterial endocarditis, osteomyelitis, opportunistic infection/hospital acquired infection (HAI) in immunocompromised patients or due to antibiotics
Inflammatory
Inflammation, surgical trauma, allergic reaction, graft rejection, transfusion reaction, hematoma, pancreatitis, atelectasis
Thrombosis
Deep vein thrombosis, pulmonary embolism
Vascular
Cerebral infarction, subarachnoid hemorrhage, myocardial infarction, surgical site ischemia, flap necrosis, bowel ischemia or infarction
Drugs
Drug induced fever, malignant hyperthermia, alcohol or drug (baclofen, steroid) withdrawal syndrome
Miscellaneous
Dehydration, neoplastic fever, hyperthyroidism, hypoadrenalism
Pathophysiology of Fever The general manifestations of a febrile response includes shivering, chills, loss of appetite, malaise, anorexia, decreased secretions, absence of sweating, and an increase in blood pressure as well as heart rate [10]. Thermoregulation is a dynamic process consisting of three components. Thermosensors located at peripheral nerve endings as well as the central hypothalamus are responsible for detecting both increase and decrease in temperature. The second component consists of reflex mechanisms to control temperature; namely heat dissipating and heat generating body systems. The third component is a neuronal coronal network of neurons within the hypothalamus. These act as negative feedback response systems [11]. As discussed earlier, postoperative fever is produced by various endogenous and exogenous pyrogens which are brought about by a myriad of causes as summarized in Table 1. The final reaction is brought about by stimulation of the hypothalamus, or more specifically at the organum vasculosum of the laminae terminalis. This area synthesizes prostaglandin E2 in response to these pyrogens, and this in turn releases cyclic adenosine monophosphate. This acts as a neurotransmitter which results in fever [12]. Fever is essentially a sequence of negative feedback, in which phases of chill, fever and flush occur depending on the stimulation of various mechanisms [13].
Etiology of Postoperative Fever Postoperative fever is a common event in patients who undergo major surgery. The incidence may range from 10 to 40 % [14], and maybe due to both infectious and noninfectious causes. More commonly postoperative fever is a
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benign event, with only a small percentage being due to an infection. The literature describes a mnemonic for remembering the causes of postoperative fever, the ‘5W’Wind, Water, Wound, Weins/Wings and Wonder drugs [15]. Ansari [16] divided the occurrence of postoperative infection into several time periods as immediate (within 24 h), acute (24–72 h), subacute or delayed (within 1st week). Jadwani et al. [17] also included intraoperative fever into this classification. The different causes of postoperative fever to be suspected during these time periods have been summarised in Table 2. The most common causes of post operative fever have been described in detail as follows.
Inflammatory Causes Inflammation is the normal human body response to any form of damage to cells. The mediators of any inflammatory response include the various cytokines like prostaglandins and leukotrienes. Miyawaki et al. [9] concluded that following maxillofacial surgery, there is an elevation in the levels of various cytokines, most notably interleukin 6 (IL-6). The elevation of plasma IL-6 correlates significantly with a rise in core body temperature following major surgical procedure, however, plasma interleukin 3 and tumour necrosis factor alpha did not significantly correlate with change in temperature. The incidence of post operative fever due to inflammatory causes largely depends upon the duration of the surgery, intraoperative transfusion, pre-existing infection and preoperative antibiotics [10]. Fever developing in patients who underwent organ transplant, grafting or
J. Maxillofac. Oral Surg. Table 2 Classification based upon time of onset and probable causes for fever Etiology
Infection
Time of onset Intra-operative
Immediate (within 24 h)
Acute (24–72 h)
Subacute or delayed (\1 week)
Preoperative infection
Clostridium perfringens or streptococcal group A infection
Surgical site infection, aspiration pneumonia, UTI, catheter associated infections, otitis media
Surgical site infection, UTI, infected prosthesis or graft, subacute bacterial endocarditis
Surgical trauma, transfusion reaction, subarachnoid haemorrhage
Atelectasis, graft rejection, allergy, pancreatitis
Graft rejection
Inflammation
Drugs
Anesthetic agents
Drug reaction, malignant hyperthermia
Drug fever
Drug or alcohol withdrawal
Vascular
Myocardial infarction, organ infarct
Fat embolism, myocardial infarction
DVT
DVT, pulmonary embolism, cavernous sinus thrombosis
Others
Heat insulation
hyperthyroidism
Hypoadrenalism, dehydration
Dehydration
reconstruction procedure is suggestive of graft rejection or infection [18]. Infection Infection is a common cause of postoperative fever. Although the majority of postoperative fever is benign in nature and more of an inflammatory response, an infectious etiology cannot be ruled out, especially in prolonged fever episodes. Most authors consider that extensive workups on patients with postoperative fever in search of an infectious etiology are a waste of resources [14, 19]. Various toxins produced by microorganisms act as exogenous pyrogens which cause rise in body temperature. Enterotoxins produced by staphylococcus aureus and superantigens by streptococcal species are common examples of pyrogenic toxins [20]. Nosocomial infections or hospital acquired infections (HAI) are to be dreaded in the postoperative setting, due to their virulence and resistance to antibiotics. Common pathogens isolated in the affected patients in several studies are coagulase-negative staphylococci, Staphylococcus aureus, Enterococcus species, Candida species, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter species, Acinetobacter baumannii, Klebsiella oxytoca and other multidrug resistant microorganisms such as methicillin resistant staphylococcus aureus [21–23].
Table 3 Drugs causing fever Common agents
Rare agents
Antibiotics Amphotericin B
Cimetidine
Anti tubercular drugs
Antitubercular drugs
Cephalosporins
Vancomycin
Penicillin
Nitrofurantoin
Sulfonamides
Tetracyclins
Anesthetic agents and analgesics Barbiturates
Cocaine
Procainamide
Halothane (general anesthetic)
Salicylates
Non steroidal anti inflammatory drugs (NSAIDS)
Chemotherapeutic agents Asparginase
Hydroxyurea
Bleomycin Cardiovascular drugs Methyldopa
Streptokinase
Quinidine sulphate
Hydralazine
Others Antihistamines
Allopurinol
Phenytoin
Azathioprine Diuretics Heparin Propylthiouracil Succinylcholine Baclofen and steroids (withdrawl symptom)
Dehydration Fever due to dehydration and vice versa is a phenomenon seen more often in neonates and infants [24–26]. Dehydration is a common problem seen in patients who underwent maxillofacial surgery due to inadequate intraoperative
and perioperative fluid management, diarrhoea and vomiting, difficulty in oral intake and patient noncompliance. Dry mouth and skin, decreased urine output, thirst, cardiovascular and neurological changes are indicative of dehydration fever in post-operative patients [27].
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Drugs
Fever Specific to Oral and Maxillofacial Surgery
Adverse and unwanted drug reactions may result in fever, especially in the immediate postoperative period. Fever may also be the presenting symptom of drug allergy [28]. Drug induced fever or ‘‘drug fever’’ is also seen accompanying the administration of certain drugs, most notably beta lactam antibiotics. Based upon the literature review and frequency of drug used during post operative period Table 3 provides a summary of drugs that may cause fever following their use [16, 17, 29–37]. Another drug induced reaction which is although rare but life threatening, associated with general anesthetic agents and/or succinylcholine is known as malignant hyperthermia (MH). MH is predominantly seen with administration of succinylcholine (77 % cases), halothane [60 %] and other general anesthetic agents with the incidence rate of approximately 1:15,000 among children and 1:50,000 in adults [38]. MH presents with an autosomal dominant inheritance pattern and predilection for males. MH is considered to be abnormal distribution of myoplasmic calcium (Ca2?). Clinical features include tachycardia, high fever, tachypnea, cardiac dysrhythmia, muscle rigidity (most frequently in masseter muscle producing trismus), cyanosis and death in severe and unattended cases [39, 40]. Drug-induced fever may also be the result of a delayed hypersensitivity reaction (type IV) and its characteristics resemble those of an allergic reaction. The onset of fever is usually after 7–10 days of drug administration, high variations, disappears soon after discontinuation of the culprit drug and recurs when drug is given to the patient again [30, 31].
Surgical procedures of maxillofacial region pose similar challenge to the immune response of the body and other factors already discussed in this article. There is no data suggesting any significant risk of post operative fever after maxillofacial procedure as compared to the surgeries of other parts of the body, however, few studies have highlighted some distinct etiopathogenesis in dental and maxillofacial surgery. Use of compressed air and air rotor handpiece in third molar extractions has shown significant risk of mediastinitis and subcutaneous emphysema where fever can be one of the presenting symptoms [44–46]. Infective endocarditis is another serious complication following minor or major surgical procedures in post operative period which should be ruled out based upon the medical history and cardiovascular examination [47]. Fever in the intraoperative period can be seen in patients with preoperative fever due to severe infections like Ludwig’s angina or extensive space infections surrounding a non reduced fracture which may also induce bacteremia on manipulation during surgery [48]. Another rare but life threatening complication is toxic shock syndrome (TSS) resulting from Staphylococcus aureus infection where fever is a common presenting symptom. TSS has been reported following nasal surgery, sinus surgery and other facial cosmetic procedures with strong association between nasal packs and splints and risk of TSS [49–52]. Low grade fever (approximately 38 °C) is a common finding after orthognathic surgery which usually subsides in first 48 h [53]. Gordon et al. [54] have shown that the severity of mandibular fractures and patient general health status correlates with the postoperative inflammatory complications. Bone grafts, mini plates and screws can produce inflammatory response or may become infected. Any patient presenting with localized symptoms and/or fever should be suspected for possible graft infection or allergic reaction and appropriate radiographic and microbiological tests should be carried out. Post operative fever is also associated with donor site morbidity [55]. Certain procedures like rib graft harvesting [56] and anterior iliac bone harvesting [57] are commonly used as adjuncts to various maxillofacial procedures and now use indwelling catheters for local post operative analgesia. Skin around the catheter site should be dressed every day and the catheter should be removed within 48 h, as their prolonged use could lead to infection and thereby fever. Maintaining the oral wound is a great challenge to the surgeon and for the patient as the mucosa is mobile and fragile, oral cavity harbours large microflora (both pathognomic and non-pathognomic), unsatisfactory
Other Causes Other causes of fever during post-operative period include malignancy arising due to cytokines (tumour necrosis factor TNF, interleukins 1 and 6 and interferon IFN) produced either by host macrophages in response to tumour, or sometimes by the tumour itself. The cytokines act on hypothalamus similar to prostaglandins causing elevation in the thermostatic set point [41]. Endocrine conditions such as hyperthyroidism or thyroid storm, hypoadrenalism may produce fever. Rise in core temperature can be indicative of deep vein thrombosis (DVT), pulmonary embolism, myocardial infarction and bowel ischemia are other possible serious complications during post-operative period. Atelectasis is considered to be an etiological factor by some authors [16, 17] however, other studies contradicts any correlation between post operative fever and developing atelectasis [42, 43].
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dressing techniques and regular contamination of the wound with saliva, water and food. Systemic antibiotic prophylaxis, preoperative local antiseptics and perioperative irrigation techniques have proved to be successful in reducing risk of surgical site infection [58–60]. A good anti microbial mouthwash has to be a mandate in all surgical procedures carried out intraorally [61]. Even in patients who have local, regional or free flaps and subjected to a nasogastric feeding tube, it is vital to maintain the oral hygiene so as to prevent infection and wound breakdown intraorally. Significant incidence of fever after palatoplasty has been reported. The author noted that the hydration was an important factor in development of post operative fever. Non weaned patients had larger fever volume as compared to weaned patients in first 48 h suggesting the importance of oral feed [62]. Similarly, another study reveals strong correlation of post operative temperature with the age of the patient of less the 24 months [63]. These findings strongly indicate that hydration and nutritional support is the major challenge in maxillofacial patients due to intraoral wound and inability to eat. Several scientific literatures have been published regarding incidence of malignant hyperthermia in dentomaxillofacial procedures, including lethal ones. With the advent of dantrolene sodium in the management of the MH, the mortality has been reduced from 80 to 10 % [64–68].
Consequences and Complications of Post-Operative Fever Fever causes rise in basal metabolic rate, increased oxygen demand, increased heart rate. As already discussed, high temperature may also induce dehydration in children. Associated symptoms such as chills, rigors, malaise can be quiet distressing to the operated patient. It is considered that for every rise of 1 °C above 37 °C, there is approximately 13 % increase in oxygen consumption. High fever can aggravate pre-existing cardiac, cerebrovascular, or pulmonary insufficiency and can induce mental changes in patients with organic brain disease. Children with a history of febrile or non febrile seizure should be treated immediately to reduce fever although it is unclear what triggers the febrile seizure and no correlation has been established between absolute temperature elevation and onset of a febrile seizure in susceptible children [1].
Management Core body temperature higher than 40° C is considered to be harmful and demand active intervention [69].
Lesperance et al. [14] conducted a prospective observational study of 1,032 postsurgical patients to determine the incidence and utility of extensive postoperative fever evaluations. 23.7 % of their patients experienced postoperative fever, out of which in 18 patients it was due to a postoperative infection. However the authors claim that 50 % of the diagnosis could have been made solely by clinical examination. They came to a conclusion that postoperative fever is common and evaluation should be focussed on clinical examination and no laboratory investigations are necessary in low risk patients within 72 h of surgery. Other studies confirm that routine blood cultures are also unnecessary in the early postoperative fever patient [11, 70, 71]. Laboratory and imaging studies should therefore only be used if necessary, depending on the history and physical examination. Blood cultures should be reserved for patients with pre-existing medical comorbidities or at an increased risk for infection. It is the point to emphasize that the proper history and thorough clinical examination should suffice to elicit the cause of fever and to decide whether treatment is indicated in the presenting situation. Treatment of postoperative fever includes cooling down procedures, various drugs to control body temperature, and specific treatment of the cause. It is necessary to arrive at a definitive diagnosis before beginning any form of therapy, however, fever up to 72 h are to be expected. Common physical cooling methods include sponging and bed fans; while more radical methods include sponging with alcohol, hypothermic mattresses or ice packs [17]. Methods like intraperitoneal lavage of cool fluid, gastric lavage or enemas with iced water and extraperitoneal circulation should be reserved for emergency situations. Monitoring of body temperature is, of course, necessary to avoid overzealous cooling [13]. Non-steroidal anti-inflammatory drugs (NSAID) include aspirin and its congeners act by inhibiting the synthesis of prostaglandins via the cyclooxygenase pathway. They are the most widely used drugs to control fever. Several studies state superiority of one NSAID over others or comparative efficiency of various combinations of these agents. Ibuprofen and paracetamol (acetaminophen) have been widely used and are considered to be safe and effective in febrile patients [72–75]. Fever due to infectious cause may require modification in antibiotic therapy depending on the culture and sensitivity examination. Surgical site infection can be prevented as well as controlled by antimicrobial dressings and irrigation with povidone iodine or chlorhexidine, however, few cases may warrant re-exploration and surgical debridement while, necrotic or infected graft should be removed. HAI and multidrug resistant microorganisms should be treated aggressively with appropriate
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antimicrobials such as cephalosporins, aminoglycoside or carbapenem [76, 77]. Other more specific causes require more specific approach in conjunction with antipyretic therapy, for instance, corticosteroids and antihistamine for allergic drug reactions [78], dantrolene sodium in malignant hyperthermia [65–67], antiepileptic drugs and benzodiazepines in epilepsy with febrile seizures [79] and anticoagulant prophylaxis for deep vein thrombosis [80]. In depth discussions of such conditions are however, beyond the scope of this article.
Conclusion In conclusion, fever in the postoperative patients is a common benign occurrence in any form of surgery, including maxillofacial surgery. However, an occurrence of fever should not be underestimated as it may indicate a more sinister underlying pathology. A specific guideline towards the management of such patients is necessary in every clinical setting to ensure optimal care towards the patients that entrust their health and well-being into the surgeon’s hands. Acknowledgments The authors affirm that they have no financial affiliation (e.g., employment, direct payment, stock holdings, retainers, consultantships, patent licensing arrangements or honoraria), or involvement with any commercial organization with direct financial interest in the subject or materials discussed in this manuscript, nor have any such arrangements existed in the past 3 years. Conflict of interest
The authors deny any conflict of interest.
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