Perioperative management of anticoagulation is a critical aspect of patient care. Virchow’s triad, consisting of hypercoagulability, stasis, and endothelial injury, explains the increased risk of venous thromboembolism (VTE) in the perioperative period. Surgical patients often experience all three components: tissue damage activates the coagulation cascade, immobility leads to blood stasis, and vascular manipulation causes endothelial disruption. These factors collectively elevate the risk of deep vein thrombosis and pulmonary embolism, necessitating effective prophylaxis strategies. At the same time, bleeding must be controlled during surgery to maintain hemodynamic stability. Anesthesia and surgery teams must carefully consider the use of anticoagulants such as enoxaparin in the perioperative period, as well as the potential stoppage of ongoing anticoagulant therapy.

Enoxaparin, a low molecular weight heparin (LMWH), acts by enhancing the inhibitory effect of antithrombin III on factor Xa and thrombin. This mechanism effectively reduces the risk of VTE without significantly increasing bleeding complications. Studies have shown that prophylactic use of enoxaparin can decrease the incidence of VTE by up to 50% in surgical patients, making it a valuable tool in perioperative thromboprophylaxis.

The indications for perioperative enoxaparin use include prophylaxis in high-risk surgical patients and bridging therapy for those on long-term anticoagulation. Timing is crucial: for prophylactic doses, the last dose should be administered at least 12 hours before the procedure. For therapeutic doses, a minimum of 24 hours should elapse between the last dose and surgery. Postoperatively, enoxaparin can typically be resumed 12-24 hours after minor surgery, but for major procedures with high bleeding risk, resumption may be delayed up to 48-72 hours.

Drug interactions between enoxaparin and anesthesia agents are an important consideration. While direct interactions with anesthetics are limited, the combination of enoxaparin with neuraxial anesthesia (spinal or epidural) requires careful timing to minimize the risk of spinal hematoma. The FDA recommends that catheter placement or removal should be delayed for at least 12 hours after prophylactic enoxaparin doses and 24 hours after therapeutic doses. Conversely, postprocedural enoxaparin should not be administered sooner than 4 hours after catheter removal.

Other considerations when administering enoxaparin during anesthesia include potential interactions with drugs that affect hemostasis. Non-steroidal anti-inflammatory drugs (NSAIDs) can increase the risk of bleeding when used concurrently with enoxaparin. Additionally, both enoxaparin and certain antibiotics like trimethoprim can elevate potassium levels, necessitating close monitoring of serum electrolytes. Renal function is another critical factor, as enoxaparin is primarily eliminated through the kidneys. Patients with impaired renal function may require dose adjustments or extended intervals between the last dose and surgical intervention to prevent excessive anticoagulation.

In conclusion, the use of enoxaparin in the perioperative period requires a delicate balance between thromboprophylaxis and bleeding risk. Anesthesia providers must be aware of the timing considerations, potential drug interactions, and patient-specific factors that influence the safe administration of enoxaparin. Close collaboration between surgical, anesthesia, and pharmacy teams is essential to optimize patient outcomes and minimize complications associated with perioperative anticoagulation management.

References

1. Douketis JD, Spyropoulos AC, Spencer FA, et al. Perioperative management of antithrombotic therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e326S-e350S. doi:1378/chest.11-2298
2. Horlocker TT, Vandermeuelen E, Kopp SL, Gogarten W, Leffert LR, Benzon HT. Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (Fourth Edition). Reg Anesth Pain Med. 2018;43(3):263-309. doi:1097/AAP.0000000000000763
3. Falck-Ytter Y, Francis CW, Johanson NA, et al. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e278S-e325S. doi:1378/chest.11-2404
4. Garcia DA, Baglin TP, Weitz JI, Samama MM. Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e24S-e43S. doi:1378/chest.11-2291
5. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest. 2016;149(2):315-352. doi:1016/j.chest.2015.11.026
6. Douketis JD, Spyropoulos AC, Duncan J, et al. Perioperative Management of Patients With Atrial Fibrillation Receiving a Direct Oral Anticoagulant. JAMA Intern Med. 2019;179(11):1469-1478. doi:1001/jamainternmed.2019.2431

Obstructive sleep apnea (OSA) is a common sleep disorder characterized by repeated episodes of upper airway collapse during sleep, leading to breathing pauses and reduced blood oxygen levels. The prevalence of OSA has increased over time, with recent studies indicating that it affects a significant portion of the adult population. According to a systematic review, the prevalence of OSA, defined as ≥5 apnea or hypopnea events per hour, ranges from 9% to 38% in the general adult population, with higher rates in men, older adults, and individuals with obesity. In some elderly groups, the prevalence can be as high as 90% in men and 78% in women. Because OSA negatively impacts long-term health and increases the risk of complications during anesthesia, refining treatment is an important focus of some medical research. The recent approval of Zepbound for treating obstructive sleep apnea represents a major step forward.

Traditionally, the primary treatment for moderate to severe OSA has been continuous positive airway pressure (CPAP) therapy. CPAP involves wearing a mask during sleep that delivers pressurized air to keep the airway open. While effective, CPAP adherence can be challenging for many patients. Other treatments include oral appliances, positional therapy, and in some cases, surgical interventions. However, the landscape of OSA treatment is evolving.

On December 20, 2024, the U.S. Food and Drug Administration (FDA) approved Zepbound® (tirzepatide) as the first medication for the treatment of moderate to severe obstructive sleep apnea in adults with obesity. Zepbound is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. It works by activating receptors of hormones secreted from the intestine, which reduces appetite and food intake. By promoting weight loss in patients with obesity, Zepbound can indirectly improve OSA symptoms.

The efficacy of Zepbound for OSA was demonstrated in the SURMOUNT-OSA phase 3 clinical trials. These studies evaluated Zepbound (10 mg or 15 mg) in adults with obesity and moderate to severe OSA, both with and without positive airway pressure (PAP) therapy. In patients not using PAP therapy, Zepbound reduced breathing disruptions by an average of 25 events per hour, compared to 5 events per hour with placebo. For those on PAP therapy, Zepbound led to 29 fewer breathing disruptions per hour, versus 6 with placebo. After one year of treatment, 42% of adults on Zepbound without PAP therapy and 50% of those on Zepbound with PAP therapy experienced remission or mild, non-symptomatic OSA, compared to 16% and 14% on placebo, respectively.

While Zepbound shows promising results for the treatment of obstructive sleep apnea, it is important to consider its potential risks and complications. Common side effects include nausea, diarrhea, vomiting, constipation, abdominal pain, and injection site reactions. More serious side effects, though less common, can include severe gastrointestinal issues, pancreatitis, gallbladder problems, hypoglycemia (especially when combined with insulin or sulfonylureas), and kidney damage. Additionally, Zepbound carries a boxed warning for the potential risk of thyroid C-cell tumors, based on animal studies.

In conclusion, the approval of Zepbound represents a significant advancement in the treatment of obstructive sleep apnea, particularly for patients with obesity. Its dual mechanism of promoting weight loss and directly improving OSA symptoms offers a novel approach to managing this prevalent sleep disorder. However, as with any medication, the benefits of Zepbound must be weighed against its potential risks. Patients considering Zepbound for OSA should consult with their healthcare providers to determine if it is an appropriate treatment option based on their individual health profile and medical history.

References

1. Senaratna CV, Perret JL, Lodge CJ, et al. Prevalence of obstructive sleep apnea in the general population: A systematic review. Sleep Med Rev. 2017;34:70-81. doi:10.1016/j.smrv.2016.07.002
2. Food and Drug Administration. FDA Approves First Medication for Obstructive Sleep Apnea. Published December 20, 2024. Accessed January 11, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-first-medication-obstructive-sleep-apnea
3. Eli Lilly and Company. FDA approves Zepbound® (tirzepatide) as the first and only prescription medicine for moderate-to-severe obstructive sleep apnea in adults with obesity. Published December 20, 2024. Accessed January 11, 2025. https://investor.lilly.com/news-releases/news-release-details/fda-approves-zepboundr-tirzepatide-first-and-only-prescription
4. Baptist Health. Zepbound Side Effects: What You Need to Know. Published August 30, 2024. Accessed January 11, 2025. https://www.baptisthealth.com/blog/weight-management/zepbound-side-effects
5. Drugs.com. Zepbound Side Effects: Common, Severe, Long Term. Updated December 30, 2024. Accessed January 11, 2025. https://www.drugs.com/sfx/zepbound-side-effects.html

While modern anesthesia is very safe, anesthesia adverse events, or complications from anesthesia unrelated to a patient’s underlying medical condition, remain. These can include nausea, vomiting, confusion, neurotoxicity, and respiratory complications, all of which can worsen patient outcomes.¹ In order to predict how a patient might respond to anesthesia, or to infer what predisposed a patient to an adverse event after the fact, researchers look to biomarkers—any measurable substance or molecule that is indicative of a disease or health outcome. Recently, researchers have identified several promising biomarkers for various anesthesia adverse events, including the few that are outlined below.
Emergence agitation (EA), sometimes known as emergence delirium, is a state of restlessness, disorientation, and incoherence that can set in as a patient wakes up from general anesthesia.² It can lead to respiratory and circulatory problems, in addition to physical injury to patients and their caregivers.³ A team of researchers from China aimed to identify biomarkers significantly altered in the blood of patients who experienced EA.³ They found a total of 12 biomarkers significantly elevated in the EA patient group, most of which are involved in chemical reactions of fatty acids and lipids. For example, one of the biomarkers, a molecule called decanoylcarnitine, is involved in a host of essential physiological processes, including some that take place in the brain. These biomarkers, the researchers suggest, could underlie the pathology of EA and potentially serve as targets for treatments aiming to reduce the incidence of anesthesia adverse events.
In some cases, biomarkers can indicate that anesthesia may not to blame for adverse postoperative outcomes. Researchers conducted a meta-analysis of trials studying biomarkers of inflammation caused by surgery.⁴ The biomarkers included the immune system proteins IL6, IL10, and tumor necrosis factor alpha and were measured in over 1,600 patients of various ages and surgery types across more than 20 trials. They found that although inflammatory biomarker levels rise following surgery, there was no difference in inflammation depending on whether propofol or sevoflurane was used. This indicates that the type of anesthesia may not have influenced inflammation.
It is important to note that biomarkers can be substances or signals other than the levels of a certain molecule in the blood. A May 2024 publication in the journal Anesthesiology⁵ described how researchers measured patients undergoing general anesthesia using an electroencephalogram (EEG), a test that captures electrical activity in the brain, in an effort to see if there might be any observable differences in those who experienced postoperative delirium, a significant change in behavior or cognition typically considered more severe than EA.⁶ Of the 151 patients evaluated, all of whom were 70 years or older, 50 patients, or 33%, developed postoperative delirium. EEGs were performed the day before surgery (baseline) and as anesthesia-induced unconsciousness set in. On average, compared with the baseline, patients with postoperative delirium had lower intensity alpha waves—a type of brainwave associated with a relaxed state—while on anesthesia during the operative phase. This could indicate that EEG biomarkers obtained at the beginning of anesthesia induction could enable the early identification of patients at risk of developing postoperative delirium.

References
 

1. Steadman, J., Catalani, B., Sharp, C. & Cooper, L. Life-threatening perioperative anesthetic complications: major issues surrounding perioperative morbidity and mortality. Trauma Surg. Acute Care Open 2, e000113 (2017), DOI: 10.1136/tsaco-2017-000113

2. Lee, S.-J. & Sung, T.-Y. Emergence agitation: current knowledge and unresolved questions. Korean J. Anesthesiol. 73, 471 (2020), DOI: 10.4097/kja.20097

3. Mi, X. et al. Identification of Serum Biomarkers Associated With Emergence Agitation After General Anesthesia in Adult Patients: A Metabolomics Analysis. Front. Med. 9, 828867 (2022), DOI: 10.3389/fmed.2022.828867

4. O’Bryan, L. J. et al. Inflammatory Biomarker Levels After Propofol or Sevoflurane Anesthesia: A Meta-analysis. Anesth. Analg. 134, 69 (2022), DOI: 10.1213/ANE.0000000000005671

5. Pollak, M. et al. Electroencephalogram Biomarkers from Anesthesia Induction to Identify Vulnerable Patients at Risk for Postoperative Delirium. Anesthesiology 140, 979–989 (2024), DOI: 10.1097/ALN.0000000000004929

6. Menser, C. & Smith, H. Emergence Agitation and Delirium: Considerations for Epidemiology and Routine Monitoring in Pediatric Patients. Local Reg. Anesth. 13, 73 (2020), DOI: 10.2147/LRA.S181459

A mechanical ventilator, also known as a respirator or breathing machine, provides life-saving support for patients with respiratory failure. However, the efficacy and safety of this intervention can be compromised by gas leakage, which occurs when anesthetic or medical gases unintentionally escape from the ventilation system or anesthesia equipment. Therefore, applying effective strategies to prevent gas leakage during mechanical ventilation is essential for optimizing patient care and outcomes.

A gas leakage can originate from several points within the mechanical ventilation system. Ventilator circuit connections, particularly those between the ventilator and the patient interface, are frequent culprits. In invasive mechanical ventilation—where a tube is inserted into the patient’s airway through the mouth, nose, or directly into the trachea—one common source of leakage is the endotracheal tube cuff. This small inflatable balloon, located near the end of the tube, can allow air to escape if it is inadequately inflated or damaged. On the other hand, in non-invasive ventilation, leaks are more common, often resulting from a poor mask fit or inadequate seal (1).

When gas leakage occurs during mechanical ventilation, it can severely impact the ventilation process, which involves moving air in and out of the lungs. Ventilation is determined by the respiratory rate (the number of breaths a person takes per minute) multiplied by the tidal volume (the amount of air moved in and out of the lungs with each breath) (2). Although minor leaks may not significantly affect ventilation, larger leaks can reduce the delivered tidal volume. This can lead to patient-ventilator asynchrony, a condition where the ventilator fails to work in harmony with the patient’s natural breathing efforts, resulting in inadequate oxygenation, impairing the removal of carbon dioxide from the body, and worsening respiratory failure.

To prevent gas leakage and its associated complications, proper adjustment of the patient interface and pressurization levels in the mechanical ventilation system is crucial. This involves ensuring the correct assembly of ventilator components, secure connections, and proper tubing management. Additionally, modern ventilators are equipped with intrinsic systems that detect and compensate for pressure and volume changes, further minimizing the risk of leaks.

In invasive ventilation, the management of the endotracheal tube plays a pivotal role in leak prevention. Proper tube placement, coupled with maintaining appropriate cuff pressure, is critical to preventing both over- and under-inflation, which can lead to leaks or tracheal damage (3). In non-invasive ventilation, ensuring a well-fitted mask and adjusting the headstrap tension can significantly reduce gas leakage (4).

Furthermore, advanced ventilators are now equipped with built-in leak detection features and compensation technologies, which ensure the patient receives the correct amount of air or oxygen even in the presence of leaks. These technologies typically employ pressure control and

volume control compensation algorithms. Pressure control compensation maintains a set pressure during each breath, increasing the inspiratory flow when a leak is detected to preserve that target pressure. In contrast, volume control compensation focuses on delivering a specific tidal volume, compensating for any air lost during leaks by delivering additional air. While both strategies are effective, pressure control compensation often offers superior leak management. Investigations into how different ventilators handle these algorithms can guide clinicians in choosing machines that better minimize risks associated with gas leaks (5).

In conclusion, preventing gas leakage during mechanical ventilation is vital to ensuring effective respiratory support for patients. By maintaining proper equipment management, applying appropriate preventive strategies, and utilizing modern ventilator technologies, clinicians can significantly reduce the risks posed by gas leaks.

References

1. Oto, J., Chenelle, C. T., Marchese, A. D., & Kacmarek, R. M. (2013). A comparison of leak compensation in acute care ventilators during noninvasive and invasive ventilation: a lung model study. Respiratory Care, 58(12), 2027-2037.

2. Carpio, A. L. M., & Mora, J. I. (2023). Ventilator management. In StatPearls [Internet]. StatPearls Publishing.

3. Fallatah, S. M., Al-metwalli, R. R., & Alghamdi, T. M. (2021). Endotracheal tube cuff pressure: An overlooked risk. Anaesthesia, Pain & Intensive Care, 25(1), 88-97.

4. Mehta, S., McCool, F. D., & Hill, N. S. (2001). Leak compensation in positive pressure ventilators: a lung model study. European Respiratory Journal, 17(2), 259-267.

5. De Luca, A., Sall, F. S., & Khoury, A. (2017). Leak compensation algorithms: the key remedy to noninvasive ventilation failure?. Respiratory Care, 62(1), 135-136.