Postoperative fever: A Practical Guide to Assessment and Management

As an intern, one of the first reflexes learnt is most likely ordering blood cultures in case of fever (second only to administering a fluid bolus for hypotension). However, postoperative fever, especially in the first few days after surgery, is often benign (1,2) and does not require the same aggressive approach. Multiple studies indicate that it is frequently over-investigated and over-treated (4,7). This blog post attempts to give guidance on how to deal with postoperative fever according to the following questions:

1) Why postoperative fever is often benign?

2) How to differentiate benign postoperative fever from pathological causes?

3) What workup should be done for postoperative fever?

1) Why postoperative fever is often benign?

Postoperative fever is common, occurring in 14% to 90% of patients, depending on the type of surgery (3,4). In most cases, this fever is considered a benign reaction to the surgery (1-4). Burns and tissue damage trigger the release of cytokines such as interleukin-1, interleukin-6 and tumor necrosis factor-alpha (4). These cytokines lead to a rise in prostaglandin levels, disrupting hypothalamic thermoregulation (4) and causing a low-grade fever (5). Additionally, macrophage activation, which helps clear extravasated blood, might contribute to prostaglandin production and temperature elevation (2). In general, the bigger the surgery, the higher the chances of postoperative fever (4).

2) How to differentiate benign postoperative fever from pathological causes?

As mentioned above, benign postoperative fever is a low-grade rise in body temperature occurring generally in the first 48 hours after surgery. One way to differentiate this from pathological causes of postoperative fever is by how postoperative fever is defined. While several definitions are circulating (3,7), the Standardised Endpoints in Perioperative Medicine Initiative provides a consensus definition focused on infection-related fever (8). They define postoperative fever as a core body temperature > 38.5 more than 24 hours after operation, with two readings within a 12 hour period (8). Apart from adapting this definition, some other factors can guide the diagnostic approach:

I. Timing

While some authors suggest that timing is the key factor distinguishing benign from pathological postoperative fever (2,9), real-world data paint a more nuanced picture. For instance, in a study of 133 postoperative fever episodes following elective colorectal surgery, infectious causes were identified in 16% of cases on postoperative day 2, 20% between day 3 and 6 and 46% after day 6 (10). Furthermore, a large cohort of 1073 orthopedic surgery patients found no significant difference in the stratified daily temperature patterns between those with infection and those with ongoing inflammation (6). Similarly, among 40 neurosurgical patients with fever deemed benign, only half experienced a temperature spike within the first 48 hours (7). Nevertheless, timing remains a useful tool for narrowing the differential diagnosis of postoperative fever, as illustrated in the table below (1,3,9):

Postoperative Fever: Timing-Based Differential Diagnosis Chart Highlighting Causes Across Different Timeframes

II. History

A basic patient history can highlight specific risk factors for postoperative fever. Medical background may point to risks such as impaired host defense (immunosuppression, …), indwelling devices, or endocrine disorders (adrenal insufficiency, thyrotoxicosis) whereas social history may flag a possible drug or alcohol withdrawal (4).

III. Intervention

Preoperative: Pre-existing infection, ICU admission prior to surgery, …

Perioperative:

• Use of blood products during surgery

• Perioperative medications: A systematic review of case reports found that propofol, morphine, beta-lactam antibiotics and anti-coagulants were most commonly involved in drug-induced fever (11). Although classically thought to occur after 1 to 2 weeks (4), most cases in this review developed within the first few postoperative days (11).

• Type of surgery: The extent and nature of the procedure influence fever risk. Larger surgeries are associated with higher rates of postoperative fever (1,12,13). Besides, clean-contaminated surgeries carry a greater risk of bacterial contamination than clean procedures (4). Additionally, specific surgical details - such as dural opening in neurosurgery - can increase the likelihood of fever due to aseptic meningitis or CSF leakage (12).

IV. Vital signs

Some common sense rules:

• Benign postoperative fever rarely exceeds 38.9°C whereas temperatures above 41°C suggest drug fever, malignant hyperthermia, or neuroleptic malignant syndrome (5).

• Hemodynamic instability, elevated lactate or high SOFA score should raise suspicion for infectious causes (13).

• Relative bradycardia is often cited as a hallmark of drug-induced fever (4), though no standardized definition exists (11).

3) What workup should be done for postoperative fever?

Postoperative fever

The following flowchart outlines a step-by-step algorithm to assess postoperative fever:

Remarks:

I. While fever often triggers the reflex to panculture, a thorough physical examination is far more diagnostic (5). Blood cultures, for example, yield a diagnosis in only 0 to 5% of cases, whereas a physical exam, with or without targeted additional tests, achieves a diagnostic accuracy of about 75% (2, 14).

II. Use of inflammatory markers such as CRP or white blood cell count to distinguish infection from other causes of postoperative fever is supported by minimal evidence (8). Even procalictonin was considered insufficiently accurate by the consensus workgroup of the Standardised Endpoints in Perioperative Medicine Initiative (8).

III. Historically, atelectasis has been cited as a cause of early postoperative fever. However, multiple studies have found no good physiological or clinical evidence to support this claim (15).

IV. Further investigations can consist of cultures of blood, urine and sputum (5), as well as focused imaging or additional blood tests such as lipase, troponin or uric acid (9). As colonization of the urinary tract, particularly after catheterization, is frequently misclassified as a true urinary tract infection, urine cultures should only be obtained in presence of symptoms, hemodynamic instability or in neutropenic patients (5).

References:

1. Maday KR, Hurt JB, Harrelson P, Porterfield J. Evaluating postoperative fever. JAAPA. 2016 Oct;29(10):23-8.

2. Lesperance R, Lehman R, Lesperance K, et al. Early postoperative fever and the "routine" fever work-up: results of a prospective study. J Surg Res. 2011 Nov;171(1):245-50.

3. Abdelmaseeh TA, Azmat CE, Oliver TI. Postoperative Fever. 2023 Jun 4. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–.

4. Burke L. Postoperative fever: a normal inflammatory response or cause for concern. J Am Acad Nurse Pract. 2010 Apr;22(4):192-7.

5. Nohra E, Appelbaum RD, Farrell MS, et al. Fever and infections in surgical intensive care: an American Association for the Surgery of Trauma Critical Care Committee clinical consensus document. Trauma Surg Acute Care Open. 2024 Jun 3;9(1):e001303.

6. Uçkay I, Agostinho A, Stern R, et al. Occurrence of fever in the first postoperative week does not help to diagnose infection in clean orthopaedic surgery. Int Orthop. 2011 Aug;35(8):1257-60. doi: 10.1007/s00264-010-1128-z. Epub 2010 Sep 25.

7. Goyal-Honavar A, Gupta A, Manesh A, et al. A prospective evaluation of postoperative fever in adult neurosurgery patients in the COVID-19 era. J Clin Neurosci. 2022 Sep;103:26-33.

8. Barnes J, Hunter J, Harris S, et al. Systematic review and consensus definitions for the Standardised Endpoints in Perioperative Medicine (StEP) initiative: infection and sepsis. Br J Anaesth. 2019 Apr;122(4):500-508.

9. Stephenson C, Mohabbat A, Raslau D, et al. Management of Common Postoperative Complications. Mayo Clin Proc. 2020 Nov;95(11):2540-2554.

10. da Luz Moreira A, Vogel JD, et al. Fever evaluations after colorectal surgery: identification of risk factors that increase yield and decrease cost. Dis Colon Rectum. 2008 May;51(5):508-13.

11. Afra F, Aboutalebzadeh M, Tayefeh S, et al. Drug-induced fever in post-surgical patients: a systematic review of case reports. Ther Adv Drug Saf. 2025 May 8;16:20420986251335825.

12. Noma M, Nakajima K, Nakamoto H, et al. Impact of dural opening on noninfectious postoperative fever in spinal surgery: a propensity-matched retrospective study. Eur Spine J. 2025 Nov 19.

13. Lee SM, Shim H. Classification of postoperative fever patients in the intensive care unit following intra-abdominal surgery: a machine learning-based cluster analysis using the Medical Information Mart for Intensive Care (MIMIC)-IV database, developed in the United States. Acute Crit Care. 2025 May;40(2):293-303.

14. Subramanian M, Hirschkorn C, Eyerly-Webb SA, et al. Clinical Diagnosis of Infection in Surgical Intensive Care Unit: You're Not as Good as You Think! Surg Infect (Larchmt). 2020 Mar;21(2):122-129.

15. Stein H, Denning J, Ahmed H, et al. Debunking a mythology: Atelectasis is not a cause of postoperative fever. Clin Imaging. 2025 Jan;117:110358.