J. Maxillofac. Oral Surg.

(Apr–June 2015) 14(2):154–161

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 / Published online: 14 January 2014
Ó Association of Oral and Maxillofacial Surgeons of India 2014

Abstract hospital setting to ensure optimal care towards the patients

Purpose The aim of this paper is to review the patho- during post operative period.
physiology of thermoregulation mechanism, various causes
of fever after maxillofacial surgery and the different Keywords Drug fever
Maxillofacial infection

treatment protocols advised in the literature. Maxillofacial surgery
Postoperative fever
Pyrogen
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 Introduction
post operative period. Several factors are responsible for
fever after the maxillofacial surgery, inflammation and Postoperative pain and fever are among the most common
infection being the commonest. However, other rare causes complaints after maxillofacial surgery. Despite being the
such as drug allergy, dehydration, malignancy and endo- most frequently encountered clinical sign, there is general
crinological disorders, etc. should be ruled out prior to any dilemma among medical and nursing staff about the vari-
definite diagnosis and initiate the treatment. Proper history ous terminologies used for the rise in body temperature.
and clinical examination is an essential tool to predict the Fever is defined as an elevation of body temperature that
causative factors for fever. Common cooling methods like exceeds the normal daily variation and occurs in conjunc-
tepid sponging are usually effective alone or in conjunction tion with an increase in the hypothalamic set point. A fever
with analgesics to reduce the temperature. of [41.5 °C ([106.7 °F) is called hyperpyrexia. Unlike
Conclusion Fever is a common postoperative complaint fever, hyperthermia is characterized by an uncontrolled
and should not be underestimated as it may indicate a more increase in body temperature that exceeds the body’s
serious underlying pathology. A specific guideline towards ability to lose heat without any change in hypothalamic set
the management of such patients is necessary in every point. Core body temperature of higher than 101.5° Fahr-
enheit or 38.5° Celsius develops when exogenous or
endogenous pyrogens stimulate the hypothalamus to
A. Christabel
R. Sharma
R. Manikandhan

P. Anantanarayanan
N. Elavazhagan develop a higher than normal thermal set point [1].
Department of Oral and Maxillofacial Surgery, Meenakshi Exogenous pyrogens originate from outside the body and
Ammal Dental College and Hospital, Maduravoyal, include microbes and their various toxins and products.
Chennai 600 095, Tamil Nadu, India
Endogenous pyrogens are derived internally, and include
R. Sharma (&) various febrile mediators like cytokines and prostaglandins
Nandan Apartment, C-72, Sarojini Marg, C-Scheme, [2]. Exogenous pyrogens typically stimulate the production
Jaipur 302001, Rajasthan, India of endogenous pyrogens. However, certain endogenous
e-mail: ravisharma_19@yahoo.com
molecules such as complement, bile acids, lymphocyte
P. Subash derived molecules and various antigen-antibody complexes
Renai Medicity, Kochi, Kerala, India may also induce the production of endogenous pyrogens [3].

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Fever is for the most part beneficial to the patient and Table 1 Causes of fever
clinician as it alerts one to the disease process and it must Infective Surgical site infection, urinary tract infection (UTI),
be qualified and verified in accordance to the etiology and pneumonia, foreign body [graft/implant] infection,
the symptoms in order to institute prompt treatment [4]. septicaemia, sinusitis, otitis media, catheter
Fever has also been postulated to be protective against associated infection, meningitis, bacterial
endocarditis, osteomyelitis, opportunistic
allergic sensitisation and atopic asthma in children [5, 6]. infection/hospital acquired infection (HAI) in
In the field of surgery, especially during the postopera- immunocompromised patients or due to antibiotics
tive period, fever is beneficial as a predictive tool to detect Inflammatory Inflammation, surgical trauma, allergic reaction,
the onset of any complications [7]. Also, it is a sign that the graft rejection, transfusion reaction, hematoma,
host is putting up a defence against the onset of infection pancreatitis, atelectasis
[8]. However excessive fever causes severe stress to the Thrombosis Deep vein thrombosis, pulmonary embolism
patient which may hamper postoperative recovery [9]. Vascular Cerebral infarction, subarachnoid hemorrhage,
myocardial infarction, surgical site ischemia, flap
This review article discusses the pathophysiology, eti-
necrosis, bowel ischemia or infarction
ology and treatment approach for post operative fever after
Drugs Drug induced fever, malignant hyperthermia, alcohol
maxillofacial surgery. 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, benign event, with only a small percentage being due to an
decreased secretions, absence of sweating, and an increase infection. The literature describes a mnemonic for
in blood pressure as well as heart rate [10]. remembering the causes of postoperative fever, the ‘5W’-
Thermoregulation is a dynamic process consisting of Wind, Water, Wound, Weins/Wings and Wonder drugs
three components. Thermosensors located at peripheral [15]. Ansari [16] divided the occurrence of postoperative
nerve endings as well as the central hypothalamus are infection into several time periods as immediate (within
responsible for detecting both increase and decrease in 24 h), acute (24–72 h), subacute or delayed (within 1st
temperature. The second component consists of reflex week). Jadwani et al. [17] also included intraoperative
mechanisms to control temperature; namely heat dissipat- fever into this classification. The different causes of post-
ing and heat generating body systems. The third component operative fever to be suspected during these time periods
is a neuronal coronal network of neurons within the have been summarised in Table 2. The most common
hypothalamus. These act as negative feedback response causes of post operative fever have been described in detail
systems [11]. as follows.
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 Inflammatory Causes
Table 1. The final reaction is brought about by stimulation
of the hypothalamus, or more specifically at the organum Inflammation is the normal human body response to any
vasculosum of the laminae terminalis. This area synthe- form of damage to cells. The mediators of any inflamma-
sizes prostaglandin E2 in response to these pyrogens, and tory response include the various cytokines like prosta-
this in turn releases cyclic adenosine monophosphate. This glandins and leukotrienes. Miyawaki et al. [9] concluded
acts as a neurotransmitter which results in fever [12]. Fever that following maxillofacial surgery, there is an elevation
is essentially a sequence of negative feedback, in which in the levels of various cytokines, most notably interleukin
phases of chill, fever and flush occur depending on the 6 (IL-6). The elevation of plasma IL-6 correlates signifi-
stimulation of various mechanisms [13]. cantly with a rise in core body temperature following major
surgical procedure, however, plasma interleukin 3 and
tumour necrosis factor alpha did not significantly correlate
Etiology of Postoperative Fever with change in temperature.
The incidence of post operative fever due to inflam-
Postoperative fever is a common event in patients who matory causes largely depends upon the duration of the
undergo major surgery. The incidence may range from 10 surgery, intraoperative transfusion, pre-existing infection
to 40 % [14], and maybe due to both infectious and non- and preoperative antibiotics [10]. Fever developing in
infectious causes. More commonly postoperative fever is a patients who underwent organ transplant, grafting or

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Table 2 Classification based upon time of onset and probable causes for fever
Etiology Time of onset
Intra-operative Immediate (within 24 h) Acute (24–72 h) Subacute or delayed (\1 week)

Infection Preoperative Clostridium perfringens or Surgical site infection, aspiration Surgical site infection, UTI, infected
infection streptococcal group A pneumonia, UTI, catheter associated prosthesis or graft, subacute
infection infections, otitis media bacterial endocarditis
Inflammation Surgical trauma, transfusion Atelectasis, graft rejection, allergy, Graft rejection
reaction, subarachnoid pancreatitis
haemorrhage
Drugs Anesthetic Drug reaction, malignant Drug fever Drug or alcohol withdrawal
agents hyperthermia
Vascular Myocardial Fat embolism, myocardial DVT DVT, pulmonary embolism,
infarction, infarction cavernous sinus thrombosis
organ infarct
Others Heat insulation hyperthyroidism Hypoadrenalism, dehydration Dehydration

reconstruction procedure is suggestive of graft rejection or Table 3 Drugs causing fever

infection [18]. Common agents Rare agents

Antibiotics
Infection
Amphotericin B Cimetidine
Anti tubercular drugs Antitubercular drugs
Infection is a common cause of postoperative fever.
Cephalosporins Vancomycin
Although the majority of postoperative fever is benign in
Penicillin Nitrofurantoin
nature and more of an inflammatory response, an infectious
Sulfonamides Tetracyclins
etiology cannot be ruled out, especially in prolonged fever
Anesthetic agents and analgesics
episodes. Most authors consider that extensive workups on
Barbiturates Cocaine
patients with postoperative fever in search of an infectious
Procainamide Halothane (general anesthetic)
etiology are a waste of resources [14, 19]. Various toxins
Salicylates Non steroidal anti
produced by microorganisms act as exogenous pyrogens inflammatory drugs (NSAIDS)
which cause rise in body temperature. Enterotoxins pro-
Chemotherapeutic agents
duced by staphylococcus aureus and superantigens by
Asparginase Hydroxyurea
streptococcal species are common examples of pyrogenic
Bleomycin
toxins [20].
Cardiovascular drugs
Nosocomial infections or hospital acquired infections
Methyldopa Streptokinase
(HAI) are to be dreaded in the postoperative setting, due to
Quinidine sulphate Hydralazine
their virulence and resistance to antibiotics. Common
Others
pathogens isolated in the affected patients in several studies
Antihistamines Allopurinol
are coagulase-negative staphylococci, Staphylococcus
Phenytoin Azathioprine
aureus, Enterococcus species, Candida species, Esche-
Diuretics
richia coli, Pseudomonas aeruginosa, Klebsiella pneumo-
niae, Enterobacter species, Acinetobacter baumannii, Heparin
Klebsiella oxytoca and other multidrug resistant microor- Propylthiouracil
ganisms such as methicillin resistant staphylococcus aureus Succinylcholine
[21–23]. Baclofen and steroids
(withdrawl symptom)

Dehydration
and perioperative fluid management, diarrhoea and vom-
Fever due to dehydration and vice versa is a phenomenon iting, difficulty in oral intake and patient noncompliance.
seen more often in neonates and infants [24–26]. Dehy- Dry mouth and skin, decreased urine output, thirst, car-
dration is a common problem seen in patients who under- diovascular and neurological changes are indicative of
went maxillofacial surgery due to inadequate intraoperative 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, Surgical procedures of maxillofacial region pose similar
especially in the immediate postoperative period. Fever challenge to the immune response of the body and other
may also be the presenting symptom of drug allergy [28]. factors already discussed in this article. There is no data
Drug induced fever or ‘‘drug fever’’ is also seen accom- suggesting any significant risk of post operative fever after
panying the administration of certain drugs, most notably maxillofacial procedure as compared to the surgeries of
beta lactam antibiotics. Based upon the literature review other parts of the body, however, few studies have high-
and frequency of drug used during post operative period lighted some distinct etiopathogenesis in dental and max-
Table 3 provides a summary of drugs that may cause fever illofacial surgery. Use of compressed air and air rotor
following their use [16, 17, 29–37]. handpiece in third molar extractions has shown significant
Another drug induced reaction which is although rare risk of mediastinitis and subcutaneous emphysema where
but life threatening, associated with general anesthetic fever can be one of the presenting symptoms [44–46].
agents and/or succinylcholine is known as malignant Infective endocarditis is another serious complication fol-
hyperthermia (MH). MH is predominantly seen with lowing minor or major surgical procedures in post opera-
administration of succinylcholine (77 % cases), halothane tive period which should be ruled out based upon the
[60 %] and other general anesthetic agents with the medical history and cardiovascular examination [47].
incidence rate of approximately 1:15,000 among children Fever in the intraoperative period can be seen in patients
and 1:50,000 in adults [38]. MH presents with an auto- with preoperative fever due to severe infections like Lud-
somal dominant inheritance pattern and predilection for wig’s angina or extensive space infections surrounding a
males. MH is considered to be abnormal distribution of non reduced fracture which may also induce bacteremia on
myoplasmic calcium (Ca2?). Clinical features include manipulation during surgery [48].
tachycardia, high fever, tachypnea, cardiac dysrhythmia, Another rare but life threatening complication is toxic
muscle rigidity (most frequently in masseter muscle pro- shock syndrome (TSS) resulting from Staphylococcus
ducing trismus), cyanosis and death in severe and unat- aureus infection where fever is a common presenting
tended cases [39, 40]. symptom. TSS has been reported following nasal surgery,
Drug-induced fever may also be the result of a delayed sinus surgery and other facial cosmetic procedures with
hypersensitivity reaction (type IV) and its characteristics strong association between nasal packs and splints and risk
resemble those of an allergic reaction. The onset of fever is of TSS [49–52].
usually after 7–10 days of drug administration, high vari- Low grade fever (approximately 38 °C) is a common
ations, disappears soon after discontinuation of the culprit finding after orthognathic surgery which usually subsides
drug and recurs when drug is given to the patient again [30, in first 48 h [53]. Gordon et al. [54] have shown that the
31]. severity of mandibular fractures and patient general health
status correlates with the postoperative inflammatory
complications. Bone grafts, mini plates and screws can
Other Causes produce inflammatory response or may become infected.
Any patient presenting with localized symptoms and/or
Other causes of fever during post-operative period include fever should be suspected for possible graft infection or
malignancy arising due to cytokines (tumour necrosis allergic reaction and appropriate radiographic and micro-
factor TNF, interleukins 1 and 6 and interferon IFN) pro- biological tests should be carried out.
duced either by host macrophages in response to tumour, or Post operative fever is also associated with donor site
sometimes by the tumour itself. The cytokines act on morbidity [55]. Certain procedures like rib graft harvesting
hypothalamus similar to prostaglandins causing elevation [56] and anterior iliac bone harvesting [57] are commonly
in the thermostatic set point [41]. Endocrine conditions used as adjuncts to various maxillofacial procedures and
such as hyperthyroidism or thyroid storm, hypoadrenalism now use indwelling catheters for local post operative
may produce fever. Rise in core temperature can be analgesia. Skin around the catheter site should be dressed
indicative of deep vein thrombosis (DVT), pulmonary every day and the catheter should be removed within 48 h,
embolism, myocardial infarction and bowel ischemia are as their prolonged use could lead to infection and thereby
other possible serious complications during post-operative fever.
period. Atelectasis is considered to be an etiological factor Maintaining the oral wound is a great challenge to the
by some authors [16, 17] however, other studies contradicts surgeon and for the patient as the mucosa is mobile and
any correlation between post operative fever and devel- fragile, oral cavity harbours large microflora (both
oping atelectasis [42, 43]. pathognomic and non-pathognomic), unsatisfactory

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dressing techniques and regular contamination of the Lesperance et al. [14] conducted a prospective observa-
wound with saliva, water and food. Systemic antibiotic tional study of 1,032 postsurgical patients to determine the
prophylaxis, preoperative local antiseptics and periopera- incidence and utility of extensive postoperative fever
tive irrigation techniques have proved to be successful in evaluations. 23.7 % of their patients experienced postop-
reducing risk of surgical site infection [58–60]. A good anti erative fever, out of which in 18 patients it was due to a
microbial mouthwash has to be a mandate in all surgical postoperative infection. However the authors claim that
procedures carried out intraorally [61]. Even in patients 50 % of the diagnosis could have been made solely by
who have local, regional or free flaps and subjected to a clinical examination. They came to a conclusion that
nasogastric feeding tube, it is vital to maintain the oral postoperative fever is common and evaluation should be
hygiene so as to prevent infection and wound breakdown focussed on clinical examination and no laboratory inves-
intraorally. tigations are necessary in low risk patients within 72 h of
Significant incidence of fever after palatoplasty has been surgery. Other studies confirm that routine blood cultures
reported. The author noted that the hydration was an are also unnecessary in the early postoperative fever patient
important factor in development of post operative fever. [11, 70, 71].
Non weaned patients had larger fever volume as compared Laboratory and imaging studies should therefore only be
to weaned patients in first 48 h suggesting the importance used if necessary, depending on the history and physical
of oral feed [62]. Similarly, another study reveals strong examination. Blood cultures should be reserved for patients
correlation of post operative temperature with the age of with pre-existing medical comorbidities or at an increased
the patient of less the 24 months [63]. These findings risk for infection. It is the point to emphasize that the
strongly indicate that hydration and nutritional support is proper history and thorough clinical examination should
the major challenge in maxillofacial patients due to intra- suffice to elicit the cause of fever and to decide whether
oral wound and inability to eat. treatment is indicated in the presenting situation.
Several scientific literatures have been published Treatment of postoperative fever includes cooling down
regarding incidence of malignant hyperthermia in dento- procedures, various drugs to control body temperature, and
maxillofacial procedures, including lethal ones. With the specific treatment of the cause. It is necessary to arrive at a
advent of dantrolene sodium in the management of the MH, definitive diagnosis before beginning any form of therapy,
the mortality has been reduced from 80 to 10 % [64–68]. 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
Consequences and Complications of Post-Operative with alcohol, hypothermic mattresses or ice packs [17].
Fever Methods like intraperitoneal lavage of cool fluid, gastric
lavage or enemas with iced water and extraperitoneal cir-
Fever causes rise in basal metabolic rate, increased oxygen culation should be reserved for emergency situations.
demand, increased heart rate. As already discussed, high Monitoring of body temperature is, of course, necessary to
temperature may also induce dehydration in children. avoid overzealous cooling [13].
Associated symptoms such as chills, rigors, malaise can be Non-steroidal anti-inflammatory drugs (NSAID) include
quiet distressing to the operated patient. It is considered aspirin and its congeners act by inhibiting the synthesis of
that for every rise of 1 °C above 37 °C, there is approxi- prostaglandins via the cyclooxygenase pathway. They are
mately 13 % increase in oxygen consumption. High fever the most widely used drugs to control fever. Several studies
can aggravate pre-existing cardiac, cerebrovascular, or state superiority of one NSAID over others or comparative
pulmonary insufficiency and can induce mental changes in efficiency of various combinations of these agents. Ibu-
patients with organic brain disease. Children with a history profen and paracetamol (acetaminophen) have been widely
of febrile or non febrile seizure should be treated imme- used and are considered to be safe and effective in febrile
diately to reduce fever although it is unclear what triggers patients [72–75].
the febrile seizure and no correlation has been established Fever due to infectious cause may require modification
between absolute temperature elevation and onset of a in antibiotic therapy depending on the culture and sensi-
febrile seizure in susceptible children [1]. tivity examination. Surgical site infection can be prevented
as well as controlled by antimicrobial dressings and irri-
gation with povidone iodine or chlorhexidine, however,
Management few cases may warrant re-exploration and surgical
debridement while, necrotic or infected graft should be
Core body temperature higher than 40° C is considered to removed. HAI and multidrug resistant microorganisms
be harmful and demand active intervention [69]. should be treated aggressively with appropriate

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antimicrobials such as cephalosporins, aminoglycoside or 9. Miyawaki T, Maede S, Koyama Y, Fukuoka R, Shimada M

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