Hospitalization costs and resource allocation in cholecystectomy with use of intravenous versus oral acetaminophen

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Hospitalization costs and resource allocation in cholecystectomy with use of intravenous versus oral acetaminophen


Hansen, R. N., Pham, A. T., Böing, E. A., Lovelace, B., Wan, G. J., Thomas, D. A., & Fontes, M. L. (2017). Hospitalization costs and resource allocation in cholecystectomy with use of intravenous versus oral acetaminophen. Current Medical Research and Opinion. doi: 10.1080/03007995.2017.1412301

Context and Motivation

This study compares the use of intravenous (IV) acetaminophen to oral acetaminophen as adjunct analgesics in patients undergoing cholecystectomy. The primary focus was on evaluating outcomes like hospital length of stay (LOS), costs, opioid use, and rates of postoperative complications. The motivation behind the research was the high incidence of intolerable side effects from opioids and the increasing interest in multimodal pain management approaches.

Key Concepts and Definitions

  • Cholecystectomy: Surgical removal of the gallbladder.
  • Acetaminophen (APAP): A medication used to treat pain and fever, available in IV and oral forms.
  • Morphine Equivalent Dose (MED): A way to quantify the potency of opioids by converting the dose to an equivalent amount of morphine.

Main Findings

The research found that IV acetaminophen usage in cholecystectomy was associated with a shorter hospital LOS by 0.42 days, reduced hospitalization costs by $1,045, a decrease in the mean daily MED by 2 mg, and lower rates of respiratory depression and nausea/vomiting compared to oral acetaminophen.

Data Sources

Data for the retrospective analysis was obtained from the Premier Database, covering the period from January 1, 2012, to September 30, 2015, which includes details from over 800 member hospitals across the U.S.

Methodological Approach

The study employed a retrospective cohort analysis. The outcomes were measured using multivariable logistic regression for binary outcomes and instrumental variable regressions for continuous outcomes. Adjustments were made for patient demographics, clinical risk factors, and hospital characteristics.

Evaluation of the Study


  1. Large and Diverse Sample: Utilizing data from the Premier Database encompassing a significant portion of U.S. inpatient hospitalizations enhances the generalizability of the findings.
  2. Robust Analytical Techniques: The use of advanced statistical methods, including multivariable logistic regression and instrumental variable regression, helps to control for confounding variables and reduce the effects of potential biases.
  3. Relevant Clinical Outcomes: The study focused on clinically meaningful outcomes such as hospital length of stay, costs, opioid use, and postoperative complications, which are critical for assessing the effectiveness of pain management strategies.


  1. Retrospective Design: The inherent limitations of a retrospective study include potential biases in data collection and the inability to control for all confounding variables, which might affect the reliability of the results.
  2. Dependency on Billing Data: Relying on hospital charge data to infer medication administration can introduce inaccuracies, as charge entries do not necessarily reflect actual clinical usage.
  3. Lack of Randomization: Without random assignment of patients to treatment groups, there are potential uncontrolled differences between the groups that could influence the outcomes.

Potential Biases

  • Selection Bias: There might be inherent differences between the patients who were administered IV versus oral acetaminophen that are not fully accounted for by the statistical adjustments.
  • Instrumentation Bias: Using the quarterly rate of IV acetaminophen use as an instrument assumes that this rate is correlated only with the choice of acetaminophen form and not with other unmeasured confounders.

Overall Impact

The study provides valuable evidence suggesting that IV acetaminophen may be more effective than oral acetaminophen in reducing hospital stay lengths, costs, and opioid use in cholecystectomy patients. These findings could influence clinical practice by supporting the integration of IV acetaminophen into multimodal pain management protocols, particularly in surgical settings where reducing opioid consumption is a priority.

Furthermore, the study highlights the importance of considering the route of administration in the effectiveness of pain management strategies. It contributes to the ongoing discussion about optimizing perioperative care to improve patient outcomes and reduce healthcare resource utilization.

However, given the study’s limitations, particularly its retrospective design, there is a need for prospective randomized trials to confirm these results and provide stronger evidence for causality. Such studies could further validate the benefits of IV acetaminophen and potentially lead to changes in clinical guidelines for postoperative pain management.

Future Directions and Recommendations

1. Prospective Randomized Trials:

To further solidify the findings, prospective randomized controlled trials (RCTs) are necessary. These trials would allow for a better assessment of causality and help control for confounding variables more effectively than retrospective studies.

2. Extended Follow-Up Periods:

Future research should consider longer follow-up periods to evaluate the long-term impacts of IV versus oral acetaminophen on patient outcomes, including recovery times and long-term pain management.

3. Expansion to Other Surgical Procedures:

Investigating the effects of IV and oral acetaminophen in other types of surgeries could provide insights into the broader applicability of these findings across various surgical disciplines.

4. Detailed Cost-Benefit Analysis:

While the study reports on hospitalization costs, a more detailed cost-benefit analysis that includes direct and indirect costs (such as patient recovery times and return to work) would provide a more comprehensive understanding of the economic impacts of IV acetaminophen use.

5. Evaluation of Patient Satisfaction:

Incorporating measures of patient satisfaction and quality of life assessments could enrich the understanding of the subjective benefits of IV versus oral acetaminophen postoperatively.

6. Study on Administration Protocols:

Research into optimal administration protocols for IV acetaminophen, such as timing and dosage relative to surgery, could optimize its efficacy and minimize side effects.

7. Interdisciplinary Approaches:

Collaboration among anesthesiologists, surgeons, pharmacists, and pain management specialists could lead to more integrated and effective pain management strategies that utilize findings from this and similar studies.

8. Implementation Studies:

Following prospective trials, implementation studies could examine the real-world effectiveness of incorporating IV acetaminophen into standard pain management protocols and its impact on clinical practice patterns.

By pursuing these directions, further research can enhance the evidence base supporting the use of IV acetaminophen in surgical pain management and potentially transform perioperative care practices to improve patient outcomes and healthcare efficiency. These steps will help to ensure that clinical practice aligns with the most robust and current evidence available, fostering improved patient care and resource utilization in healthcare settings.

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