Impact of Hypoalbuminemia on Cefoperazone/Sulbactam Induced Coagulopathy in Post-Operative Surgical Patients

The goal of this observational study is to learn whether hypoalbuminemia in post surgical patients receiving cefoperazone/sulbactam therapy poses them to the risk of developing coagulopathy. It will also study that what are the other risk factors for the development of cefoperazone/sulbactam induced coagulopathy. The main questions it aims to answer are : • Does hypoalbuminemia increase the risk of cefoperazone/sulbactam coagulopathy in post operative surgical patients?

• What is the incidence of cefoperazone/sulbactam induced coagulopathy in normoalbuminemic vs hypoalbuminemic patients.
• Does renal function, nutritional status, dose and duration of therapy affect coagulopathy development?
• What are the independent risk factors for the development of cefoperazone/sulbactam induced coagulopathy? Patients' coagulation tests will be followed during the duration of cefoperazone/sulbactam therapy to identify coagulation development.

Study Overview

• Status: Not yet recruiting
• Conditions: Cefoperazone/Sulbactam Induced Coagulopayjy

Detailed Description

This study will be conducted in the Department of Pharmacology in collaboration with the General Surgery Department of Shaikh Zayed Medical Complex, Lahore. The study population will include adult post-operative surgical patients who are on cefoperazone-sulbactam therapy for at least 72 hours and who are willing to give informed consent. Sample size was estimated using the WHO sample size calculator to compare two proportions in a prospective cohort study. It was based using incidence in a recent relevant study. The minimum sample size was determined to be 49 patients in each group i.e. hypoalbuminemic (serum albumin < 3.5 g/dl) and normoalbuminemic ( serum albumin >= 3.5 g/dl) groups (98 patients total) based on an assumed incidence of coagulopathy of 40% in hypoalbuminemic patients and 15% in normoalbuminemic patients, a 95% confidence level, a study power of 80%, and a ratio of 1:1 for exposed to unexposed patients. Including 10% for possible dropouts and incomplete follow-up increased the final sample size to 54 patients per group for a total sample size of 108 post operative patients.

Data Collection Procedure: Non-probability consecutive sampling technique will be used for data collection procedure; all eligible post-operative surgical patients admitted to the General Surgery Department and prescribed cefoperazone/sulbactam for at least 72 hours will be recruited for the study with approval from the Institutional Review Board (IRB) and informed written consent from the patients. Demographic and clinical data, such as gender, age, type of surgery, co-morbidities and indication for antibiotic therapy will be collected on a structured proforma. Laboratory studies will be performed within 24 hours of surgery and before or within 24 hours of starting cefoperazone/sulbactam and will include serum albumin, complete blood count (CBC), serum creatinine, estimated glomerular filtration rate (eGFR), prothrombin time (PT), and international normalized ratio (INR). Patients will then be divided into two groups: patients with hypoalbuminemia (serum albumin <3.5 g/dL) and patients with normal albumin levels (serum albumin ≥3.5 g/dL).

Details of nutritional status (BMI and Nutritional Risk Screening-2002 score), dosage of cefoperazone/sulbactam, duration of therapy, cumulative dose and other co-administered drugs will also be recorded. Patients will be followed up prospectively during the treatment period with cefoperazone/sulbactam. Monitoring of PT and INR will be done on Day 0 (baseline), Day 3, Day 5 and Day 7 of treatment or until the end of the treatment. Any coagulopathy (PT > 25% seconds from baseline, INR>1.5 or clinically significant bleeding due to coagulation abnormality) associated with cefoperazone/sulbactam will be recorded. All the data collected will be entered into a pre-designed data collection form and patient information will be kept confidential throughout the study process.

Statistical Analysis: Quantitative variable will be reported in the form of mean ± standard deviation for data that is normally distributed or median and interquartile range (IQR) for data that is not normally distributed. Qualitative variables will be presented as frequencies and percentages. Independent Sample t-test will be used to compare baseline characteristics of the hypoalbuminemic and normoalbuminemic patients for continuous variables with normal distribution, while Mann-Whitney U test will be used for continuous variables not normally distributed. Categorical variables will be compared between the two groups using the Chi-square test or Fisher's Exact test, as appropriate. The primary outcome, coagulopathy due to administration of cefoperazone/sulbactam will be compared between the hypoalbuminemic and normoalbuminemic cohorts by the Chi-square test. Relative Risk (RR) with 95% Confidence interval (CI) will be calculated to assess the association between hypoalbuminemia and coagulopathy. Variables that had a p value <0.20 on univariate analysis and clinically relevant covariates such as age, gender, renal dysfunction, nutritional status, duration of therapy, cumulative antibiotic dose and comorbidities will be entered into a multivariable logistic regression model to identify independent predictors of coagulopathy induced by cefoperazone/sulbactam. Adjusted Odds Ratios (AOR) will be reported with their 95% confidence intervals (CIs). All statistical analyses will use a 2-tailed p-value cut off of ≤ 0.05.

• Study Type: Observational
• Enrollment (Estimated): 108

Contacts and Locations

• Study Contact: Name: Dr. Fatima Aftab, PGR Pharmacology, FPGMI Lahore; Phone Number: +923304262819; Email: fatimaaftabkhosa1999@gmail.com
• Study Contact Backup: Name: Dr. Mudassara Yaseen HOD Pharmacology FPGMI, Lahore; Phone Number: +923334162630; Email: Drmudassarayaseen@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients will be enrolled from the Department Of General Surgery at Shaikh Zayed Hospital, Lahore who fulfill the eligibility criteria.

Description

Inclusion Criteria:

• Patients >= 18 years
• Post-operative surgical patients
• Receiving cefoperazone/sulbactam therapy for at least 72 hours.
• Willing to give informed consent

Exclusion Criteria:

• Chronic liver disease
• History of any inherited coagulation disorder
• On anticoagulant therapy
• Any massive blood loss requiring blood transfusion
• Patients who have been given Vitamin K prior to the start of cefoperazone/sulbactam therapy
• Pregnancy

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
The first group will be of normoalbuminemic post surgical patients receiving cefoperazone/sulbactam
The second group will be of hypoalbuminemic post surgical patients receiving cefoperazone/sulbactam

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Coagulopathy Development in Hypoalbuminemic post operative surgical patients receiving cefoperazone/sulbactam	Development of coagulopathy ( any one of the following : INR >1.5 , PT > 25% from baseline, clinically significant bleeding due to coagulation disorder ) in hypoalbuminemic post operative surgical pateints receiving cefoperazone/sulbactam	From the start of cefoperazone/sulbactam therapy after surgery till the completion of therapy with cefoperazone/sulbactam i.e atleast 72 hours/3days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of cefoperazone/sulbactam induced coagulopathy in normoalbuminemic and hypoalbuminemic patients	I will compare the incidence of coagulopathy in hypoalbuminemic and normoalbuminemic post operative surgical pateints receiving cefoperazone /sulbactam and will give values in percentages	From enrollment through study completion, an average of 6 months.
Association between renal function and nutritional status on cefoperazone/sulbactam induced coagulopathy development	I will study if abnormal renal function ( eGFR < 60 mL/min/1.73m2 ) and poor nutritional status ( assessed using the NRS-2002 scale ) have any affect on the development of cefoperazone/sulbactam induced coagulopathy	From the start of cefoperazone/sulbactam therapy after surgery till the completion of therapy with cefoperazone/sulbactam i.e atleast 72 hours/3days
Cumulative dose ( in grams ) of cefoperazone/sulbactam and the development of coagulopathy	It will be studied that what is the cut-off cumulative dose ( in grams ) of cefoperazone/sulbactam that is associated with the development of coagulopathy.	From the start of cefoperazone/sulbactam therapy after surgery till the completion of therapy with cefoperazone/sulbactam i.e atleast 72 hours/3days
To identify independent predictors of coagulopathy among post-surgical patients receiving cefoperazone/sulbactam by performing multivariable logistic regression	To identify independent predictors of coagulopathy among post-surgical patients receiving cefoperazone/sulbactam by performing multivariable logistic regression analysis including hypoalbuminemia, renal function, nutritional status, dose, duration of therapy, and other clinically relevant confounding factors.	From the start of cefoperazone/sulbactam therapy after surgery till the completion of therapy with cefoperazone/sulbactam i.e atleast 72 hours/3days

Collaborators and Investigators

• Sponsor: Sheikh Zayed Federal Postgraduate Medical Institute

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2027
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: August 8, 2026
• First Submitted That Met QC Criteria: August 14, 2026
• First Posted (Actual): August 19, 2026

Study Record Updates

• Last Update Posted (Actual): September 10, 2026
• Last Update Submitted That Met QC Criteria: September 5, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Protein Disorders; Hypoproteinemia; Hemic and Lymphatic Diseases; Hypoalbuminemia
• Other Study ID Numbers: TERC/SC/INT/2026/93

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No