Reversal Agents for Postoperative Urinary Retention

Overseen By Fabio Rodriguez, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: The Cleveland Clinic

Must not be taking: Anticholinergics, Antihistamines, Antidepressants, Antipsychotics

Disqualifiers: Urinary comorbidities, Neurological conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: During surgery

50 Participants Needed

Trial Summary

Do I have to stop taking my current medications for this trial?

The trial does not specify if you need to stop all current medications, but you cannot participate if you are currently using anticholinergic medications like antihistamines, phenothiazines, antidepressants, or antipsychotics.

What data supports the idea that Reversal Agents for Postoperative Urinary Retention is an effective drug?

The available research shows that sugammadex, one of the reversal agents, is more effective in reducing postoperative urinary retention compared to the combination of neostigmine and glycopyrrolate. For example, in a study involving patients who underwent hysterectomy, 24.8% of those who received neostigmine-glycopyrrolate experienced urinary retention, while only 18.3% of those who received sugammadex did. This suggests that sugammadex is associated with a lower risk of urinary retention after surgery. ^{1 2 3 4 5}

What safety data exists for reversal agents used in postoperative urinary retention?

Safety data for reversal agents like neostigmine and sugammadex indicate that neostigmine, often used with glycopyrrolate, can lead to postoperative urinary retention (POUR) due to glycopyrrolate's anticholinergic effects. Sugammadex, which does not require an anticholinergic coadministration, is associated with a lower incidence of POUR. Studies have evaluated the effects of these agents on renal biomarkers and their impact on urinary retention in various surgical settings, suggesting sugammadex may be a safer option regarding urinary retention. ^{1 2 3 5 6}

Is the drug Sugammadex a promising treatment for preventing urinary retention after surgery?

Yes, Sugammadex is a promising drug for preventing urinary retention after surgery. It does not require additional drugs to counteract side effects, unlike Neostigmine, which needs to be combined with Glycopyrrolate. Studies show Sugammadex is associated with a lower chance of urinary retention. ^{1 2 3 5 6}

What is the purpose of this trial?

This trial compares two drugs, sugammadex and neostigmine, to help adults recover from muscle relaxation after non-cardiac surgery. Sugammadex works by neutralizing the muscle relaxants directly, while neostigmine helps increase a natural substance in the body. The goal is to find out which drug is more effective.

Research Team

Kurt Ruetzler, MD

Principal Investigator

The Cleveland Clinic

Eligibility Criteria

This trial is for adults aged 65 or older who are having noncardiac surgery under general anesthesia with muscle relaxation, and will stay in the hospital overnight. They must be healthy enough (ASA status 1-3) and able to consent. People with urinary issues, severe liver or kidney disease, neurological conditions, or those on certain medications can't join.

Inclusion Criteria

I am 65 years old or older.

Informed Consent as documented by signature

I will be given medication to reverse muscle relaxation after surgery.

Exclusion Criteria

I am scheduled to have a urinary catheter placed during surgery.

I will have a catheter placed before surgery.

Presence of a sacral nerve stimulator

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Treatment

Randomized administration of either neostigmine or sugammadex for reversal of neuromuscular block during surgery

During surgery

1 visit (in-person)

Immediate Postoperative Monitoring

Monitoring of twitch responses and urinary retention in the post anesthesia care unit (PACU)

1 hour after surgery

1 visit (in-person)

Postoperative Follow-up

Monitoring for urinary retention and other outcomes on the regular ward

24 hours after surgery

3 visits (in-person)

Extended Follow-up

Data collection from electronic medical records until postoperative day 4 or discharge

Up to 4 days

Treatment Details

Interventions

• Neostigmine
• Neostigmine with glycopyrrolate
• Sugammadex

Trial Overview The study compares two drugs used to reverse muscle relaxation after surgery: Sugammadex and Neostigmine combined with glycopyrrolate. It's a randomized trial for patients given rocuronium or vecuronium during their procedure.

Participant Groups

Group I: Neostigmine Active Control 1 Intervention

Reversal of Neuromuscular Block by Neostigmine.

Group II: Sugammadex Active Control 1 Intervention

Reversal of Neuromuscular Block by Sugammadex.

Neostigmine is already approved in United States, European Union, India for the following indications:

Approved in United States as Prostigmin for:

• Myasthenia Gravis
• Reversal of Neuromuscular Blockade
• Urinary Retention

Approved in European Union as Neostigmine for:

• Myasthenia Gravis
• Reversal of Nondepolarizing Muscle Relaxants

Approved in India as Neostigmine for:

• Myasthenia Gravis
• Reversal of Neuromuscular Blockade

Who Is Running the Clinical Trial?

The Cleveland Clinic

Lead Sponsor

Trials

1,072

Recruited

1,377,000+

Findings from Research

In a study of 61,898 matched adult inpatients and 95,500 matched adult outpatients, patients who received neostigmine with glycopyrrolate for neuromuscular block reversal experienced a two-fold higher incidence of post-operative urinary retention compared to those reversed with sugammadex (5.0% vs 2.4% inpatients; 0.9% vs 0.4% outpatients).

Multivariable analysis confirmed that using neostigmine was independently associated with a greater risk of post-operative urinary retention, with odds ratios of 2.20 for inpatients and 2.57 for outpatients, indicating a significant safety concern with this reversal method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-operative urinary retention is impacted by neuromuscular block reversal agent choice: A retrospective cohort study in US hospital setting. Bash, LD., Turzhitsky, V., Mark, RJ., et al.[2023]

Glycopyrrolate, commonly used with neostigmine to reverse non-depolarizing neuromuscular blockade, has been associated with adverse effects on the genitourinary system, particularly increasing the risk of urinary retention.

This review aims to update the understanding of glycopyrrolate's impact on post-operative urinary retention, addressing gaps in previous studies that did not prioritize this outcome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glycopyrrolate and Post-Operative Urinary Retention: A Narrative Review. Low, J., Escobar, M., Baquero, S., et al.[2020]

In a study of 485 patients undergoing laparoscopic or robotic hysterectomy, those who received sugammadex had significantly lower odds of experiencing transient postoperative urinary retention (TPOUR) compared to those treated with a combination of glycopyrrolate and neostigmine (GN).

Patients treated with GN were 1.79 times more likely to be discharged with an indwelling catheter, indicating that sugammadex may be a safer option for neuromuscular reversal in this surgical context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of sugammadex on postoperative urinary retention post-laparoscopic and robotic hysterectomy with and without concomitant procedures. Dueñas-Garcia, OF., Shah, T., Fritts, L., et al.[2023]

In a study of 1,974 patients undergoing hysterectomy, the use of sugammadex for reversing neuromuscular blockade was associated with a significantly lower risk of postoperative urinary retention (POUR) compared to neostigmine-glycopyrrolate, with an odds ratio of 0.53.

The findings suggest that the lower risk of POUR with sugammadex may be due to the absence of glycopyrrolate, which is used with neostigmine and may contribute to urinary retention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sugammadex and urinary retention after hysterectomy: A propensity-matched cohort study. De Lima Laporta Miranda, ML., Ochs Kinney, MA., Bakkum-Gamez, JN., et al.[2023]

In a study of 181 patients undergoing unilateral inguinal herniorrhaphy, reversal of neuromuscular blockade with sugammadex was associated with significantly lower rates of postoperative urinary retention (POUR) compared to neostigmine/glycopyrrolate, with only 3% of patients in the sugammadex group experiencing POUR versus 15% in the neostigmine/glycopyrrolate group.

The findings suggest that using sugammadex may be a safer option for preventing POUR, which can lead to complications such as unplanned admissions or emergency room visits, although further confirmation through randomized studies is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Urinary Retention Following Inguinal Herniorrhaphy: Role of Neuromuscular Blockade Reversal. Valencia Morales, DJ., Stewart, BR., Heller, SF., et al.[2023]

Sugammadex appears to have more tolerable effects on kidney function compared to neostigmine in patients undergoing elective surgery, as indicated by differences in postoperative kidney markers like cystatin C.

Both sugammadex and neostigmine do not cause renal failure, but they can negatively affect kidney function, highlighting the importance of monitoring kidney health during and after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Sugammadex and Neostigmine on Renal Biomarkers. Isik, Y., Palabiyik, O., Cegin, BM., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Post-operative urinary retention is impacted by neuromuscular block reversal agent choice: A retrospective cohort study in US hospital setting. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Glycopyrrolate and Post-Operative Urinary Retention: A Narrative Review. [2020]

3. England pubmed.ncbi.nlm.nih.gov

The effect of sugammadex on postoperative urinary retention post-laparoscopic and robotic hysterectomy with and without concomitant procedures. [2023]

4. Bosnia and Herzegovina pubmed.ncbi.nlm.nih.gov

Sugammadex and urinary retention after hysterectomy: A propensity-matched cohort study. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Urinary Retention Following Inguinal Herniorrhaphy: Role of Neuromuscular Blockade Reversal. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Effects of Sugammadex and Neostigmine on Renal Biomarkers. [2019]