P-015 - Exploring Historical and Novel Respiratory Stimulants for Postoperative Respiratory Depression Treatment

Abstract Title: Exploring Historical and Novel Respiratory Stimulants for Postoperative Respiratory Depression Treatment

Background: Recovery following surgery is influenced by various factors, encompassing both intra- and post-operative pharmacological interventions. These interventions include medications for anesthesia, pain management, muscle relaxation, and anxiety relief. Notably, certain medications can induce respiratory depression, either independently or through additive or synergistic effects.

Recent recognition extends beyond the immediate post-operative period, highlighting sequelae that can manifest 30, 60, or even 90 days post-surgery, leading to serious morbidity and mortality (Miskovic & Lumb, 2017). However, attributing these post-hospital sequelae to peri and post-operative respiratory depression poses challenges due to the delayed onset. Consequently, the extent and gravity of the negative impact of intra- and post-operative respiratory depression often remain underestimated and underreported.

Purpose/Objectives: Given the substantial and escalating number of surgical procedures conducted annually, even a minor percentage of postoperative respiratory complications can affect a significant number of patients. In light of this, we provide a comprehensive overview of the issue, examining both historical and innovative therapeutic approaches to manage and mitigate these complications. This includes the emerging potential of peripherally acting agents that enhance respiratory drive, aiming to improve patient outcomes and reduce healthcare costs.


Methods: Data from published reviews and primary sources (in English) on the topic respiratory stimulants were reviewed and summarized. We present a succinct overview of historic and investigative novel future therapies. Past strategies, commonly referred to as 'analeptics,' primarily targeted the brain or the sympathetic subdivision of the autonomic nervous system. Examples include cocaine, ephedrine, atropine, amphetamines, strychnine, picrotoxin, tetrazoles, caffeine, and ampakines.


Results: A recent innovative physiological target is the carotid bodies, situated outside the central nervous system (CNS), thus offering the potential for respiratory efficacy without CNS-related adverse effects. At the molecular level, potassium channels present novel targets. Agonist activation of TASK-1 or -3 chemoreceptors (e.g., almitrine, doxapram) or antagonism of BK (big potassium) feedback loop channels (ENA-001) can stimulate respiration without counteracting the beneficial effects of respiratory depressants (Golder et al. 2013).

Conclusions/Implications for future research and/or clinical care: PORD and pulmonary complications are common and costly, both medically and financially. Reversing PORD for acute protection and preventing postoperative pulmonary complications (PPCs) are critical. However, utilizing a receptor antagonist to address PORD is problematic because, while it restores respiration, it also restores pain. A new pharmacological approach is needed for treating PORD and preventing PPCs by focusing on peripherally acting agents that enhance respiratory drive rather than using receptor blockers.


References: Miskovic A and Lumb AB: Postoperative pulmonary complications. Brit J Anaesth. 2017;118:317-334 [doi: 10.1093/bja/aex002. PMID: 28186222]

Golder FJ, Hewitt MM, McLeod JF. Respiratory stimulant drugs in the post-operative setting. Respir Physiol Neurobiol. 2013;189(2):395-402. [doi: 10.1016/j.resp.2013.06.010. Epub 2013 Jun 17. PMID: 23791825]