Category: Uncategorized

Disclaimer: This article is intended solely for informational and educational purposes only. It does not constitute medical advice.

Perioperative use of prothrombin complex concentrate (PCC) has become an important component of modern bleeding management for patients requiring urgent surgery or experiencing significant perioperative hemorrhage. PCC is a plasma-derived concentrate containing the vitamin K-dependent clotting factors II, VII, IX, and X. Compared with fresh frozen plasma (FFP), PCC can be administered more rapidly, requires less infusion volume, and does not require blood type matching. These characteristics allow faster correction of clotting factor deficiencies while reducing complications associated with large-volume plasma transfusions, making PCC particularly valuable when timely hemostasis is essential (1).  

The most well-established indication for PCC is the rapid reversal of warfarin anticoagulation in patients requiring emergency surgery or other urgent invasive procedures. Because warfarin prolongs the international normalized ratio (INR), patients remain at increased risk of excessive bleeding until clotting factor levels are restored. Administration of four-factor PCC together with intravenous vitamin K has consistently been shown to normalize the INR more rapidly than FFP while providing effective hemostasis. PCC also avoids the delays associated with plasma thawing and reduces the risk of transfusion-associated circulatory overload because substantially less infusion volume is required (2). 

Prothrombin complex concentrate also helps manage severe perioperative bleeding, particularly during cardiac surgery. Cardiopulmonary bypass can dilute clotting factors and impair normal coagulation, contributing to significant postoperative hemorrhage. In patients with persistent bleeding despite conventional blood component therapy, PCC rapidly replaces multiple clotting factors. Evidence indicates that PCC can reduce allogeneic blood transfusion requirements and improve bleeding control without consistently increasing mortality or major thromboembolic complications. Although much of the available evidence comes from observational studies, current findings support PCC as an effective adjunct in appropriately selected patients (3). 

Direct oral anticoagulants (DOACs) are now widely used for the prevention and treatment of thromboembolic disease, which makes perioperative management of anticoagulated patients a common clinical challenge. Although specific reversal agents are available for certain DOACs, they may not always be readily available or appropriate in every clinical setting. In these situations, PCC is commonly used to improve hemostasis before emergency surgery or during life-threatening bleeding, particularly in patients receiving factor Xa inhibitors. While PCC does not completely reverse the anticoagulant effect of these medications, clinical studies demonstrate that it can improve clot formation and contribute to effective bleeding control when rapid intervention is necessary (4).  

Despite its clinical benefits, PCC should be administered thoughtfully because it contains concentrated procoagulant factors that may increase the risk of thromboembolic events. Contemporary studies have generally reported low rates of complications such as deep vein thrombosis, pulmonary embolism, myocardial infarction, and ischemic stroke when PCC is used appropriately. Nevertheless, clinicians should carefully consider each patient’s thrombotic risk, including a history of previous thromboembolism, cardiovascular disease, malignancy, or mechanical heart valves. Weight-based dosing and laboratory assessment remain essential to achieving effective hemostasis while minimizing adverse events (4). 

Current perioperative bleeding management increasingly incorporates PCC into goal-directed transfusion strategies that combine clinical assessment with coagulation testing to guide therapy. This approach aims to rapidly correct clotting factor deficiencies while avoiding unnecessary transfusions. Although additional randomized studies are needed to define optimal dosing strategies, current evidence supports prothrombin complex concentrate as a safe, effective, and efficient therapy for urgent warfarin reversal and selected cases of severe perioperative bleeding. 

References 

1. Levy JH, Douketis J, Steiner T, Goldstein JN, Milling TJ. Prothrombin Complex Concentrates for Perioperative Vitamin K Antagonist and Non-vitamin K Anticoagulant Reversal. Anesthesiology. 2018;129(6):1171-1184. doi:10.1097/ALN.0000000000002399 

2. Sarode R, Goldstein JN, Simonian G, et al. Vitamin K Antagonist Reversal for Urgent Surgery Using 4-Factor Prothrombin Complex Concentrates: A Randomized Clinical Trial. JAMA Netw Open. 2024;7(8):e2424758. Published 2024 Aug 1. doi:10.1001/jamanetworkopen.2024.24758 

3. Roman M, Biancari F, Ahmed AB, et al. Prothrombin Complex Concentrate in Cardiac Surgery: A Systematic Review and Meta-Analysis. Ann Thorac Surg. 2019;107(4):1275-1283. doi:10.1016/j.athoracsur.2018.10.013 

4. Tanaka KA, Shettar S, Vandyck K, Shea SM, Abuelkasem E. Roles of Four-Factor Prothrombin Complex Concentrate in the Management of Critical Bleeding. Transfus Med Rev. 2021;35(4):96-103. doi:10.1016/j.tmrv.2021.06.007 

Disclaimer: This article is intended solely for informational and educational purposes only. It does not constitute medical advice.

Regional anesthesia is an important component of thoracic surgery that reduces opioid consumption and improves postoperative recovery. Among the available regional techniques providing analgesia for the chest area, thoracic paravertebral block (PVB) and serratus anterior plane block (SAPB) have emerged as commonly utilized options. Both techniques provide effective analgesia for thoracic procedures, but they differ in anatomical targets, technical complexity, and analgesic efficacy. Understanding these differences allows anesthesiologists to select the most appropriate block based on patient and surgical factors. 

Thoracic paravertebral block involves deposition of local anesthetic adjacent to the thoracic vertebral bodies within the paravertebral space. The block anesthetizes spinal nerves as they emerge from the intervertebral foramina, producing unilateral somatic and sympathetic blockade over multiple dermatomes. PVB has long been considered one of the most effective regional techniques for thoracotomy and video-assisted thoracoscopic surgery. Numerous studies have demonstrated reductions in postoperative pain scores, opioid consumption, nausea, and pulmonary complications compared with systemic analgesia alone. 

In contrast, the serratus anterior plane block is a more superficial ultrasound-guided fascial plane block. Local anesthetic is injected either superficial to or deep in the serratus anterior muscle, targeting the lateral cutaneous branches of the intercostal nerves. SAPB primarily provides analgesia to the anterolateral chest wall, making it particularly useful for minimally invasive thoracic procedures, rib fractures, and breast surgery. Because the injection occurs farther from the neuraxis and pleura, SAPB is often considered technically simpler and potentially safer than PVB. 

Comparative studies generally demonstrate superior analgesic efficacy with paravertebral block over serratus anterior plane block for thoracic surgery. Patients receiving paravertebral blocks report lower pain scores and have reduced opioid requirements during the first 24 to 48 postoperative hours. The broader dermatomal coverage and sympathetic blockade provided by PVB contribute to its effectiveness, particularly following painful procedures such as thoracotomy. Some investigations have reported analgesia approaching that of thoracic epidural analgesia while avoiding many of the hemodynamic side effects associated with epidural techniques. 

Despite its advantages, PVB presents several challenges. The procedure requires greater technical expertise and carries risks including inadvertent pleural puncture, pneumothorax, vascular puncture, and epidural spread of local anesthetic. Ultrasound guidance has improved the safety profile of the technique, but complications remain possible. In anticoagulated patients or individuals with altered thoracic anatomy, PVB may be less desirable. 

The serratus anterior plane block offers several practical advantages. Ultrasound landmarks are generally easy to identify, and the block can be performed quickly with the patient in multiple positions. Because the injection site is superficial, the risk of serious complications is relatively low. SAPB may be particularly attractive in enhanced recovery pathways where simplicity and efficiency are priorities. However, its analgesic effect may be less comprehensive, especially for procedures involving deeper thoracic structures or extensive posterior chest wall incisions. 

Current evidence suggests that paravertebral block remains the preferred regional technique when maximal analgesia is required after thoracic surgery, but serratus anterior plane block represents an effective alternative when technical limitations, patient comorbidities, or safety considerations make paravertebral block less desirable. Both techniques can significantly reduce perioperative opioid requirements and contribute to enhanced recovery after thoracic procedures. Selection should be individualized based on surgical invasiveness, patient risk factors, provider expertise, and institutional resources. 

References 

1. Yeung JH, Gates S, Naidu BV, Wilson MJ, Gao Smith F. Paravertebral block versus thoracic epidural for patients undergoing thoracotomy. Cochrane Database Syst Rev. 2016;2:CD009121. DOI: 10.1002/14651858.CD009121.pub2 
2. Elsharkawy H, Maniker R, Bolash R, Kalasbail P, Drake RL, Mariano ER. Serratus plane block: a narrative review. Reg Anesth Pain Med. 2018;43(5):493-498. DOI: 10.21037/apm-20-1542  
3. Fu Y, Zhang X, Xu H, et al. Comparison of serratus anterior plane block and thoracic paravertebral block for postoperative analgesia after thoracoscopic surgery: a meta-analysis. J Cardiothorac Vasc Anesth. 2023;37(4):1160-1168. DOI: 10.5606/tgkdc.dergisi.2024.26887 
4. Kotzé A, Scally A, Howell S. Efficacy and safety of thoracic paravertebral block in thoracic surgery: a systematic review and meta-analysis. Br J Anaesth. 2009;103(5):626-636. DOI: 10.1093/icvts/ivt551 
5. Karmakar MK. Thoracic paravertebral block. Anesthesiology. 2001;95(3):771-780. DOI: 10.1097/00000542-200109000-00033 

Prior to surgical procedures, patients undergo a preoperative evaluation to determine surgical suitability and identify risk factors that may increase the likelihood of perioperative complications. One commonly utilized component of this evaluation is the electrocardiogram (ECG), which helps detect cardiac arrythmias, structural abnormalities, or evidence of ischemia that may predispose patients to major adverse cardiac events (MACE) during or after surgery. Historically, preoperative ECGs were frequently ordered for broad patient populations, particularly older adult. However, evolving evidence has demonstrated that selective preoperative ECG screening based on clear indications and individualized evaluation is more clinically effective and cost-efficient than routine universal testing.

Earlier preoperative screening practices supported liberal ECG ordering for both minor and major surgical procedures, especially among elderly patients. This approach was largely justified by the significant morbidity and mortality associated with perioperative cardiac complications and by ability of ECGs to identify occult cardiovascular disease. A study involving more than 23,000 patients undergoing noncardiac surgery found that patients with ECG abnormalities had a 4.5-fold increased risk of cardiovascular mortality compared with patients who had normal ECG findings (Noordzij et al., 2006).  However, the study also demonstrated that the prognostic value of ECG abnormalities was substantially less significant in low- and intermediate-risk surgical procedures. Similarly, a cohort study of approximately 3,000 surgical patients reported that although preoperative ECG abnormalities were associated with postoperative cardiac complications, ECG findings provided little additional predictive value beyond information obtained through standard clinical history and physical examination (van Klei et al., 2007).

As evidence accumulated, contemporary guidelines shifted toward a more selective approach to preoperative ECG testing. The 2024 American Heart Association (AHA) guidelines stratify perioperative cardiovascular risk into low-risk (<1% risk of MACE) and elevated-risk (≥1% risk of MACE) categories. According to these guidelines, asymptomatic patients undergoing low-risk surgical procedures generally do not require a preoperative ECG regardless of age because the likelihood of perioperative cardiac complications is minimal.

For patients undergoing intermediate- or high-risk procedures, such as major vascular or thoracic surgery, the guidelines recommend a stepwise assessment that incorporates functional capacity, commonly measured in metabolic equivalents (METs). Patients with functional capacity of at least 4 METs, such as the ability to climb two flights of stairs without symptoms, are considered to have adequate exercise tolerance and often do not benefit from routine ECG screening. In contrast, known cardiovascular disease, new cardiac symptoms, significant cardiovascular risk factors, or poor functional capacity remain indications for preoperative ECG screening in patients who are undergoing elevated-risk surgery.

Overall, the role of the preoperative ECG has evolved from a strategy of routine universal screening to one centered on individualized risk stratification. Although ECGs remain valuable in high-risk populations, modern evidence-based guidelines increasingly emphasize clinical history, physical examination, and surgical risk assessment over indiscriminate testing. In addition, reducing unnecessary preoperative ECG testing helps limit false-positive findings that may lead to further invasive testing, specialist consultations, or delays in surgical scheduling. Selective screening protocols therefore improve healthcare efficiency while reducing patient anxiety and avoiding interventions unlikely to improve perioperative outcomes or overall patient safety. 

References 

1. Dobson GP. Trauma of major surgery: A global problem that is not going away. Int J Surg. 2020;81:47-54. doi:10.1016/j.ijsu.2020.07.017 
2. Noordzij PG, Boersma E, Bax JJ, et al. Prognostic value of routine preoperative electrocardiography in patients undergoing noncardiac surgery. Am J Cardiol. 2006;97(7):1103-1106. doi:10.1016/j.amjcard.2005.10.058 
3. van Klei WA, Bryson GL, Yang H, et al. The value of routine preoperative electrocardiography in predicting myocardial infarction after noncardiac surgery. Ann Surg. 2007;246(2):165 170. doi:10.1097/01.sla.0000261737.62514.63 
4. Thompson A, Fleischmann KE, Smilowitz NR, de las Fuentes L, et al. 2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM Guideline for Perioperative Cardiovascular Management for Noncardiac Surgery: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2024;150(22). doi:10.1161/CIR.0000000000001285 

Neurapraxia is a transient block in the conduction of impulses through a peripheral nerve, which results in temporary loss of motor, sensory, or mixed function without structural damage. Clinically, it presents as numbness, paresthesia, weakness, or paralysis in the distribution of the affected nerve, typically occurring shortly after regional anesthesia or surgery. Recovery is expected and is usually complete within days to weeks as conduction resumes. According to the Seddon classification, neurapraxia is the mildest form of nerve injury, defined by the absence of axonal degeneration. In the context of regional anesthesia, neurapraxia accounts for the majority of postoperative neurological symptoms (1). The reported incidence of neurapraxia ranges from 0.03% to 2.8%, reflecting variations in study design, follow-up, and the type of nerve block involved. 

Upper extremity nerve block techniques, particularly interscalene and supraclavicular brachial plexus blocks, demonstrate higher rates of neurapraxia. Prospective data from shoulder surgery patients indicate that rates of neurological symptoms consistent with neurapraxia that resolve without intervention approach 2% following interscalene block (2). This pattern likely reflects the compact organization of neural elements and limited space for anesthetic dispersion in these areas. Of note, supraclavicular blocks demonstrate slightly lower rates. Infraclavicular and axillary blocks are associated with lower incidences as well, often below 1%. This may be related to improved needle control and greater spatial separation of nerve structures in this region of the upper body. 

Lower extremity nerve blocks, including femoral, sciatic, and popliteal approaches, demonstrate lower incidence of neurapraxia overall compared to other types. Registry and observational data suggest incidences typically between 0.1% and 0.5%, with most cases resolving without sequelae (3). Continuous catheter techniques may increase the likelihood of transient nerve irritation due to prolonged exposure or mechanical factors, though persistent deficits are uncommon. Determining the cause of postoperative neurological symptoms is often challenging, as similar findings may result from the nerve block itself or from perioperative factors such as positioning, compression, and surgical manipulation 

Neuraxial anesthesia presents a distinct but related profile. Transient neurologic symptoms, such as radicular pain or dysesthesia, occur in approximately 1% to 3% of cases, depending on anesthetic choice and technique, with lidocaine historically associated with higher rates (1). These effects are generally attributed to nerve root irritation or localized anesthetic exposure within the spinal canal, rather than the focal peripheral nerve injury seen with peripheral nerve blocks. 

Large contemporary analyses indicate that clinically significant peripheral nerve injury following regional anesthesia is uncommon, occurring in fewer than 0.1% of cases. Most of these cases involve transient dysfunction rather than permanent damage (4). Differences in incidence of neurapraxia and neurological injury across nerve block types highlight the influence of anatomy, technique, and procedural context. In practice, these findings support risk stratification when selecting block approaches and reinforce the importance of ultrasound guidance, careful needle advancement, and avoiding high injection pressures. 

Neurapraxia is the most common neurological complication of nerve blocks, with incidence rates varying according to anatomical site and technique. Proximal upper extremity blocks carry relatively higher rates of transient symptoms, while distal and lower extremity approaches demonstrate a lower incidence rate. Despite this variation, outcomes are consistently favorable, supporting the continued use of regional anesthesia within a framework of careful technique and patient-specific risk assessment.

References 

1. Brull R, McCartney CJ, Chan VW, El-Beheiry H. Neurological complications after regional anesthesia: contemporary estimates of risk. Anesth Analg. 2007;104(4):965-974. doi:10.1213/01.ane.0000258740.17193.ec

2. Neal JM, Barrington MJ, Brull R, et al. The Second ASRA Practice Advisory on Neurologic Complications Associated With Regional Anesthesia and Pain Medicine: Executive Summary 2015. Reg Anesth Pain Med. 2015;40(5):401-430. doi:10.1097/AAP.0000000000000286

3. Barrington MJ, Watts SA, Gledhill SR, et al. Preliminary results of the Australasian Regional Anaesthesia Collaboration: a prospective audit of more than 7000 peripheral nerve and plexus blocks for neurologic and other complications. Reg Anesth Pain Med. 2009;34(6):534-541. doi:10.1097/aap.0b013e3181ae72e8

4. Luo T, Berecki-Gisolf J, Marshall S. Incidence of peri-operative peripheral nerve injuries associated with general and regional anaesthesia: an observational study. Anaesthesia. 2026;81(5):627-636. doi:10.1111/anae.70081

Indications for long-term opioid therapy are far narrower today than they were in the past. Historically, opioids were widely prescribed for chronic non-cancer pain under the assumption that they provided sustained relief with manageable risk. Given what is known today about the risks of opioid use, the decision to initiate long-term opioid therapy—typically defined as use beyond three months—requires a far more critical, evidence-based approach.^1,2

The primary indication for long-term opioid therapy is not a specific diagnosis but a clinical judgment that anticipated benefits in pain relief and functional improvement outweigh known risks. While the risks of long-term opioid use—including opioid use disorder, overdose, and death—are well established, high-quality evidence demonstrating sustained long-term benefit remains limited, with few randomized trials extending beyond short-term follow-up.¹ For example, for chronic non-cancer pain, including conditions like chronic low back pain, osteoarthritis, or neuropathic pain, current guidelines emphasize that opioids should only be considered as a last resort. Instead, alternative therapies are recommended to be considered first, including nonsteroidal anti-inflammatory drugs (NSAIDs), antidepressants (e.g., SNRIs), anticonvulsants (e.g., gabapentin), physical therapy, and behavioral interventions. As a result, opioids are now considered a conditional, rather than routine, option for chronic non-cancer pain.²

Despite this general lack of long-term efficacy data, there are specific clinical contexts where long-term opioid therapy remains indicated. Opioids may be appropriate when a patient has a serious illness with a poor prognosis for returning to their previous level of function, when there are specific contraindications to non-opioid therapies, or when both clinician and patient agree that the overriding goal is patient comfort.¹ Certain examples of these scenarios include pain management related to sickle cell disease, cancer-related pain treatment, palliative care, and end-of-life care—situations in which the unique therapeutic goals and the balance of benefits and risks can justify long-term opioid use.¹

When clinicians and patients consider the indications for long-term opioid therapy, it is vital to acknowledge the harms of both the overtreatment and undertreatment of pain. While the dangers of liberal opioid prescribing are well documented, some experts argue that withholding opioids from patients with high-impact chronic pain who have exhausted other alternatives can also cause harm, potentially increasing the risk of mental health crises or suicide.^2,3 Furthermore, if the clinical indication is met to initiate opioid therapy, it must be accompanied by realistic goal-setting. Before starting therapy, clinicians and patients must establish specific, measurable treatment goals for pain and function and must clearly define an exit strategy or tapering plan if the expected benefits do not materialize.¹

Ultimately, the decision to prescribe opioids long-term is highly individualized. It relies not on a rigid sequential failure of other treatments but on a careful, patient-centered assessment that ensures the specific benefits of long-term opioid therapy will meaningfully outweigh the substantial risks.

References

1. Dowell D, Ragan KR, Jones CM, Baldwin GT, Chou R. CDC clinical practice guideline for prescribing opioids for pain–United States, 2022. MMWR Recomm Rep. 2022;71(3):1–95.

2. Bicket MC, Bateman BT. Long-term opioid therapy for pain: what is known about harms–and still not known about benefits. JAMA. 2025;334(12):1057–1058.

3. Webster LR. Long-term pain therapy with opioids. JAMA. 2026 Jan 27;335(4):372–373.

The human intestinal microbiome is a complex and dynamic ecosystem that plays a central role in metabolism, immune regulation, and bioactive compound production.¹ Its composition can vary dramatically according to specific genetic and environmental factors and can be disrupted by physiological stressors, such as surgery.² Accumulating evidence demonstrates that both gastrointestinal and non-gastrointestinal surgeries significantly alter gut microbial diversity and composition, with changes observed in specific taxa that persist for weeks to months post-operation. Such alterations have been implicated in adverse outcomes, including postoperative infections and anastomotic complications. While factors such as antibiotic use, bowel preparation, nutrition, and surgical technique are known contributors to microbiome disruption, the independent role of anesthesia remains poorly understood.³ Clarifying the effects of different anesthetic agents such as sevoflurane on the intestinal microbiome is critical to improving patient outcomes.

In a 2021 experimental study, researchers investigated the effect of sevoflurane inhalational anesthesia on the intestinal microbiome by longitudinally assessing microbial changes in mice using rRNA gene sequencing. They also performed untargeted metabolomic analyses to characterize associated functional alterations. Sixteen 6–8-week-old male mice were randomly assigned to receive either 4 hours of sevoflurane anesthesia or no anesthesia, and fecal samples were collected for subsequent analysis.

Results showed sevoflurane anesthesia induced significant, time-dependent alterations in the intestinal microbiome. Principal component and principal coordinate analyses demonstrated clear differences between experimental and control groups on days 1, 3, and 7 after anesthesia, with the magnitude of contrast diminishing by day 14, a marker which suggests partial recovery. The most pronounced difference was on day 7, when the experimental group exhibited the lowest number of unique operational taxonomic units and a significant reduction in alpha diversity; this was followed by a slow trend toward restoration. Sustained compositional shifts were observed, including (semi-permanent) increases of Bacteroides, Alloprevotella, and Akkermansia bacteria and decreased Lactobacillus genera by day 14.

Further analyses revealed dynamic changes in microbial gene expression and metabolic pathways across various study time points. Differentially expressed genes were most abundant on days 3 and 14, while fewer were detected on days 1 and 7. Importantly, early alterations (day 1) were associated with pathways related to ribosomal function, nucleotide metabolism, and DNA repair. By day 7, pathways such as sphingolipid metabolism and the pentose phosphate pathway were enriched. By day 14, increased activity was observed in two-component systems, lipopolysaccharide biosynthesis, transcription machinery, and amino acid metabolism. Altogether, these findings indicate that sevoflurane anesthesia not only alters microbial composition but also induces sustained functional and metabolic reprogramming of the gut microbiome.³

Sevoflurane is believed to alter the intestinal microbiome through both direct and indirect mechanisms. Directly, in vitro studies show that sevoflurane exerts antibacterial effects against gram-positive, gram-negative, and even multidrug-resistant bacteria.⁴ Indirectly, it may influence microbial composition via the brain–gut–bacteria axis, a bidirectional communication network that links the central and enteric nervous systems with the gastrointestinal tract and its microbiota; this connection involves afferent (bottom-up) and efferent (top-down) signaling pathways.⁵

Research shows that sevoflurane anesthesia independently induces alterations in the intestinal microbiome’s composition, diversity, and metabolic function, with the most pronounced changes occurring one week after exposure. Although partial recovery was observed, persistent taxonomic and functional changes suggest anesthesia may have lasting effects on the intestinal ecosystem. These findings highlight the need to further investigate the clinical implications of anesthesia-related microbiome modulation, particularly given its potential relevance to postoperative outcomes and host systemic physiology.

References

1. Roux A, Payne SM, Gilmore MS. Microbial Telesensing: Probing the Environment for Friends, Foes, and Food. Cell Host & Microbe. 2009;6(2):115-124. https://doi.org/10.1016/j.chom.2009.07.004

2. Guyton K, Alverdy JC. The gut microbiota and gastrointestinal surgery. Nature Reviews Gastroenterology & Hepatology. 2016;14(1):43-54. https://doi.org/10.1038/nrgastro.2016.139

3. Han C, Zhang Z, Guo N, et al. Effects of Sevoflurane Inhalation Anesthesia on the Intestinal Microbiome in Mice. Frontiers in Cellular and Infection Microbiology. 2021;11. https://doi.org/10.3389/fcimb.2021.633527

4. Martínez-Serrano M, Gerónimo-Pardo M, Martínez-Monsalve A, Crespo-Sánchez MD. Antibacterial effect of sevoflurane and isoflurane. Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia. 2017;30(2):84-89. https://pubmed.ncbi.nlm.nih.gov/28198170/

5. Gracie DJ, Hamlin PJ, Ford AC. The influence of the brain–gut axis in inflammatory bowel disease and possible implications for treatment. The Lancet Gastroenterology & Hepatology. 2019;4(8):632-642. https://doi.org/10.1016/S2468-1253(19)30089-5

Methylene blue is a compound that plays both diagnostic and therapeutic roles in medicine. Originally developed as a textile dye in the late 19th century, it was one of the earliest synthetic agents used clinically. Today, methylene blue serves versatile clinical functions as a dye in imaging and as a medication in the treatment of certain hematological and hemodynamic disorders.

The primary FDA-approved use of methylene blue is the treatment of methemoglobinemia, a condition in which the iron in hemoglobin is oxidized from the ferrous (Fe²⁺) to the ferric (Fe³⁺) state. This transformation prevents normal oxygen binding and transport, leading to tissue hypoxia and cyanosis. Common causes include exposure to oxidizing agents, such as dapsone, benzocaine, and nitrates. Methylene blue functions as an artificial electron carrier within the NADPH-methemoglobin reductase pathway. It is reduced to leucomethylene blue, which donates electrons to convert methemoglobin back to functional hemoglobin. The standard treatment dose is 1 mg/kg of a 1% solution administered intravenously over several minutes, and most patients improve rapidly (1).

In addition to being used as a therapeutic medication, methylene blue is widely used as an intraoperative dye. In breast surgery, it assists in sentinel lymph node mapping by visually tracing lymphatic drainage from the tumor site. The blue-stained nodes can be selectively excised for histologic evaluation, allowing for accurate staging while minimizing tissue dissection. A meta-analysis found that methylene blue alone provides reliable detection rates comparable to radiotracer methods, making it an effective, low-cost option for many surgical centers (2). In endocrine surgery, it is also used identify parathyroid glands during parathyroidectomy. Its preferential uptake by parathyroid tissue allows surgeons to distinguish the glands from adjacent structures, reducing the risk of accidental removal or nerve injury (3).

In cardiac anesthesia and critical care, methylene blue helps manage vasoplegic syndrome, a severe complication characterized by persistent hypotension and low vascular resistance despite high-dose vasopressors. By inhibiting nitric oxide synthase and guanylate cyclase, methylene blue decreases cyclic GMP levels and restores vascular tone. Clinical studies have shown that its use can improve hemodynamics and reduce mortality in vasoplegic patients following cardiac surgery (4). Although not considered first-line therapy, it serves as a valuable rescue option when conventional treatments fail.

Although methylene blue is generally safe at therapeutic doses, clinicians should be aware of potential adverse effects. Common reactions include dizziness, mild headaches, and blue or green discoloration of the urine and skin. Serious complications can arise when methylene blue is administered with serotonergic drugs, such as selective serotonin reuptake inhibitors (SSRIs) or monoamine oxidase (MAO) inhibitors, as it possesses mild monoamine oxidase inhibitory properties. These combinations may cause serotonin syndrome, which is characterized by agitation, tremor, and hyperthermia (5). Methylene blue is also contraindicated in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency because oxidative stress can lead to hemolytic anemia. Additionally, it is contraindicated during pregnancy due to teratogenic risk.

Despite these limitations, methylene blue remains a valuable agent in perioperative medicine. Its ability to function as both a visual aid and a pharmacological treatment makes it particularly useful in complex surgical and critical care situations.

References

1. do Nascimento TS, Pereira RO, de Mello HL, Costa J. Methemoglobinemia: from diagnosis to treatment. Rev Bras Anestesiol. 2008;58(6):651-664. doi:10.1590/s0034-70942008000600011
2. Li J, Chen X, Qi M, Li Y. Sentinel lymph node biopsy mapped with methylene blue dye alone in patients with breast cancer: A systematic review and meta-analysis. PLoS One. 2018;13(9):e0204364. Published 2018 Sep 20. doi:10.1371/journal.pone.0204364
3. Dudley NE. Methylene blue for rapid identification of the parathyroids. Br Med J. 1971;3(5776):680–681.
4. Levin RL, Degrange MA, Bruno GF, et al. Methylene blue reduces mortality and morbidity in vasoplegic patients after cardiac surgery. Ann Thorac Surg. 2004;77(2):496-499. doi:10.1016/S0003-4975(03)01510-8
5. Gillman PK. CNS toxicity involving methylene blue: the exemplar for understanding and predicting drug interactions that precipitate serotonin toxicity. J Psychopharmacol. 2011;25(3):429-436. doi:10.1177/0269881109359098

Obtaining informed consent is a cornerstone of ethical medical practice, particularly in anesthesia and surgery, where risk, complexity, and uncertainty intersect. Yet even with thorough preoperative discussions, unanticipated developments—changes in anatomy, unexpected bleeding, newly discovered pathology, or equipment-related challenges—can arise once a patient is anesthetized. These moments require clinicians to balance patient autonomy, clinical judgment, and the ethical obligation to prevent harm. As perioperative medicine grows more complex, navigating patient consent when the clinical situation changes unexpectedly during anesthesia and surgery remains a critical topic in medical ethics and patient safety.

A central principle of informed consent is that patients must understand and agree to the nature, risks, benefits, and alternatives of a procedure. However, once a patient is sedated or receives general anesthesia, they are no longer able to participate in further discussion. Anesthesiologists and surgeons typically address the possibility of intraoperative changes during preoperative counseling, but the extent of that discussion varies widely. While some patients explicitly authorize “permission to proceed as necessary” for unforeseen findings, such authorization must not be interpreted as blanket consent for unrelated or elective interventions. Ethical guidelines emphasize that consent is specific to the planned procedure and its reasonably anticipated contingencies.

When the situation changes after induction of anesthesia, clinicians must determine whether immediate action is necessary to protect the patient from imminent harm or if it is more appropriate to discuss further treatment with the patient and obtain consent once the ongoing procedure is complete. If a situation is emergent—life-threatening hemorrhage, rapidly evolving instability, or a discovery that demands urgent correction—surgeons are ethically permitted to perform additional necessary interventions without new consent, guided by the principle of implied consent in emergencies. This standard is widely supported across medical ethics literature, recognizing that delaying treatment to awaken the patient or locate a surrogate could jeopardize the patient’s life or long-term health.

However, not all intraoperative discoveries justify proceeding without further consent. When the new situation is not urgent—for example, detecting a non-emergent hernia, finding a benign mass, or considering an optional repair—best practices call for pausing the operation and seeking consent from the patient’s designated surrogate decision maker. Modern perioperative workflows increasingly incorporate preoperative identification of a surrogate and real-time communication protocols to facilitate ethical decision-making when these scenarios arise. Some institutions even establish structured “intraoperative pause” procedures to enable documentation, communication, and ethical review before any unplanned intervention is undertaken.

Anesthesiologists play a crucial mediating role during such events. Because they maintain physiological control and situational awareness, they determine whether awakening the patient is safe or feasible. They also provide valuable insight into the patient’s preoperative discussions, including statements about preferences, limitations on acceptable surgical expansion, or religious and cultural considerations. Good perioperative practice emphasizes interprofessional communication, with the anesthesia team, surgeons, and nursing staff collaborating to evaluate the clinical and ethical dimensions of the new scenario.

Transparency and postoperative communication are equally essential. Regardless of the decisions made during surgery, clinicians must clearly explain to the awakened patient or their surrogate what occurred, why decisions were made, and what consequences or follow-up needs may result. This conversation is not only ethically required—it also reinforces trust and supports patient understanding during recovery. Thorough documentation in the operative note and consent record further strengthens legal and ethical accountability.

As surgical technology evolves, intraoperative findings may become more common due to advanced imaging, minimally invasive exploration, and broader access to surgical care. To meet these challenges, clinicians and institutions should ensure that informed consent conversations with the patient include explicit discussion of potential contingencies, designate a surrogate decision-maker in advance, and establish feasible protocols for obtaining intraoperative consent if the situation changes. Regular ethics training, simulation exercises, and adherence to professional guidelines can help teams respond consistently and ethically when the unexpected happens.

References

1. American Medical Association. AMA Code of Medical Ethics Opinion 2.1.1: Informed Consent. American Medical Association; 2023. https://code-medical-ethics.ama-assn.org/ethics-opinions/informed-consent

2. American Society of Anesthesiologists. Statement on Informed Consent for Anesthesia Care. ASA; 2022. https://www.asahq.org/standards-and-practice-parameters/statement-on-the-anesthesia-care-team

3. American College of Surgeons. Statements on Principles: Informed Consent. ACS; 2020.

4. Appelbaum PS. Assessment of patients’ competence to consent to treatment. N Engl J Med. 2007;357(18):1834-1840. DOI: 10.1056/NEJMcp074045

5. Beauchamp TL, Childress JF. Principles of Biomedical Ethics. 8th ed. Oxford University Press; 2019. DOI: 10.1080/15265161.2019.1665402

The perioperative management of angiotensin-converting enzyme (ACE) inhibitors is an active area of research in anesthesiology, cardiology, and perioperative medicine. ACE inhibitors are widely prescribed for hypertension, heart failure, and chronic kidney disease, yet their hemodynamic effects may complicate surgical care. A review of current literature highlights the impacts of pre-operative ACE inhibitor use on surgical outcomes.

One of the most consistently reported concerns is the increased risk of intraoperative hypotension among patients who continue ACE inhibitors up to the day of surgery. Multiple randomized trials and meta-analyses demonstrate higher rates of anesthesia-related hypotension in these patients, often requiring vasopressor support. While this hypotension does not always translate into worse postoperative outcomes, it poses challenges for intraoperative management and remains a key reason many clinicians elect to hold the medication on the morning of surgery. Despite this, some studies suggest that the hemodynamic instability associated with pre-operative ACE inhibitors is transient and may not significantly impact major surgical outcomes.

Renal outcomes appear more complex. Earlier cohort studies found an increased risk of postoperative acute kidney injury (AKI) among cardiac surgery patients taking ACE inhibitors preoperatively, likely due to altered renal autoregulation during cardiopulmonary bypass. However, more recent meta-analyses have reported a small but statistically significant reduction in AKI among patients receiving renin-angiotensin system inhibitors before surgery. These benefits seem more pronounced in noncardiac surgery populations and in patients with preexisting chronic kidney disease, suggesting that patient selection and surgical context are crucial modifiers of risk.

Emerging evidence indicates that continuation of ACE inhibitors as normal before surgery may provide mortality benefits in specific settings. Retrospective analyses of large cardiac surgery databases show that patients maintained on ACEIs have lower in-hospital mortality, reduced sepsis, and fewer postoperative complications. Some studies even suggest a dose-response relationship, with medium -dose therapy offering the most protection. Outside of cardiac surgery, population-based studies of older adults demonstrate reduced mortality and functional decline when ACE inhibitors are continued perioperatively compared with alternative antihypertensives.

Despite these promising findings, the literature is far from uniform. In coronary artery bypass grafting (CABG) patients, some studies report no significant association between preoperative ACE inhibitor use and mortality, renal failure, or long-term survival. Additionally, a few analyses note increased heart failure-related readmissions among ACE inhibitor users, raising questions about postoperative management strategies.

Given these mixed outcomes, current guideline perspectives advocate individualized decision-making. Many Enhanced Recovery After Surgery programs recommend withholding ACE inhibitors on the day of surgery to reduce hypotension risk but restarting them early in the postoperative period once hemodynamic stability is achieved. The optimal strategy likely varies based on patient comorbidities, ACE inhibitor dose, and the type of surgery.

In conclusion, the effect of pre-operative ACE inhibitor therapy on surgical outcomes is multifaceted. While continuation may reduce mortality and improve renal outcomes in select populations, it also increases the likelihood of intraoperative hypotension. Clinicians must balance these considerations and tailor decisions to each patient’s cardiovascular profile and surgical risk. Additional randomized controlled trials are needed to establish standardized perioperative protocols that optimize both safety and long-term outcomes.

References

1. Shi P, Li Z, Young N, Ji F, Wang Y, Moore P, Liu H. The effects of preoperative renin-angiotensin system inhibitors on outcomes in patients undergoing cardiac surgery. J Cardiothorac Vasc Anesth. 2013 Aug;27(4):703-9. doi: 10.1053/j.jvca.2013.01.012

2. Li WC, Kennedy AC, Potts RJ, et al. The impact of dose and discontinuation timing of preoperative ACE inhibitors on survival outcomes in cardiac surgery: A MIMIC-IV database analysis. Crit Care Med. 2023. doi: 10.1371/journal.pone.0334889

3. Wallace CM, Walker PM, Morris KP, et al. Withholding vs continuing angiotensin-converting enzyme inhibitors or angiotensin receptor blockers before surgery: a systematic review and meta-analysis. Anaesthesia. 2008;63(11):1358-1364. doi: 10.1080/07853890.2025.2566873

4. Arora P, Rajagopalam S, Ranjan R, et al. Preoperative use of ACE inhibitors/ARBs is associated with increased risk for acute kidney injury after cardiovascular surgery. Clin J Am Soc Nephrol. 2008;3(5):1266-1273. doi: 10.2215/CJN.05271107

5. Wikström B, Bäck M, Agvald-Åman M, et al. Preoperative renin-angiotensin system inhibitors linked to reduced acute kidney injury: a systematic review and meta-analysis. Kidney Int. 2015;87(3):555-564. doi: 10.1093/ndt/gfv023

Understanding how molecular physiology diverges between natural sleep and general anesthesia, which produces pharmacologic unconsciousness, is valuable clinically and for sleep research. Broadly, sleep is an active, homeostatically regulated process that engages cell type-specific transcriptional, translational, and post-translational programs, whereas general anesthesia suppresses brain activity by acting on a constellation of molecular targets, some overlapping with sleep pathways but many unique to anesthetic drugs.

At the transcriptional and proteomic level, recent single-cell and cell-type proteomics studies show that sleep need and sleep deprivation produce rapid, cell-specific changes in gene expression and phosphorylation, particularly in astrocytes and neurons of cortex, hypothalamus, and brainstem. Immediate-early genes, transcription factors related to synaptic scaling, and pathways linked to mitochondrial function and protein phosphorylation are modulated—signatures that appear tailored to restore synaptic homeostasis and metabolic balance after wakefulness. In contrast to sleep, the molecular actions of general anesthesia are better characterized at the level of receptor and ion-channel pharmacology. GABA-A receptor potentiation (propofol, volatile agents, benzodiazepines), NMDA receptor antagonism (ketamine), and modulation of two-pore K+ channels or HCN channels are canonical mechanisms of anesthesia that reduce neuronal excitability and alter synaptic transmission. These direct protein-level interactions produce rapid changes in synaptic efficacy and network synchrony that do not require the slower gene-expression cascades characteristic of physiological sleep.

Adenosine signaling and neuromodulator withdrawal are a notable point of convergence in the molecular pathways of sleep and general anesthesia. Sleep pressure is tightly linked to adenosine accumulation and downstream effects on A1/A2 receptors and neuronal excitability. Adenosine antagonists (such as caffeine) accelerate emergence from certain anesthetics in animal and human studies, implicating adenosine pathways in both sleep homeostasis and anesthesia emergence. However, whereas sleep invokes coordinated homeostatic gene programs that dissipate adenosine-linked pressure, anesthetic exposure typically produces an abrupt pharmacologic blockade of arousal circuits without engaging the same restorative transcriptional responses. Electrophysiologic correlates reflect these molecular differences. Both NREM sleep and several anesthetics show prominent slow-delta oscillations and spindles, but higher-dose anesthetic states can produce burst suppression and cortical isoelectricity—patterns not seen in physiological sleep—reflecting deeper, drug-specific suppression of cortical and thalamocortical circuit function. Molecularly, these EEG changes parallel agent-specific modulation of synaptic proteins and ion channels rather than the phased transcriptional programs seen in sleep recovery.

Clinically, these distinctions matter. Anesthetics can disrupt circadian clock gene expression and selectively affect memory consolidation by interfering with hippocampal oscillations and synaptic plasticity. Postoperative cognitive dysfunction and delirium likely arise from a complex interplay between direct drug effects on synaptic function, altered sleep architecture after surgery, and patient vulnerability such as age or neurodegenerative disease. Emerging molecular data suggest that perioperative strategies that support sleep-related restorative pathways (such as preserving NREM architecture and minimizing nocturnal circadian disruption) may mitigate cognitive sequelae after anesthesia, but prospective clinical translation remains limited.

To a limited extent, sleep and general anesthesia overlap at the level of network signatures in the brain and in some neuromodulatory systems, but they differ fundamentally in timescale and molecular depth: sleep engages coordinated, cell-specific transcriptional and proteomic responses that restore homeostasis, whereas anesthetics produce relatively rapid, receptor- and channel-mediated suppression of excitability and information integration. For anesthesiologists, integrating molecular insights with EEG and circuit-level knowledge can help tailor anesthetic choice and perioperative care to reduce cognitive risk and optimize recovery.

References

1. Jha PK, Valekunja UK, Ray S, Nollet M, Reddy AB. Single-cell transcriptomics and cell-specific proteomics reveals molecular signatures of sleep. Commun Biol. 2022;5:846. DOI: 10.1038/s42003-022-03800-3.
2. Moody OA, Zhang ER, Vincent KF, et al. The neural circuits underlying general anesthesia and sleep. Anesth Analg. 2021;132(5):1254-1264. DOI: 10.1213/ANE.0000000000005361.
3. Franks NP, Wisden W. The inescapable drive to sleep: overlapping mechanisms of sleep and sedation. Science. 2021;374(6567):556-559. DOI: 10.1126/science.abi8372.
4. Liu H, Yang Z, Chen Y, et al. Neural oscillations and memory: unraveling the mechanisms of anesthesia-induced amnesia. Front Neurosci. 2024. https://doi.org/10.3389/fnins.2024.1492103.
5. Date A, Bashir K, Uddin A, Nigam C. Differences between natural sleep and the anesthetic state. Future Sci OA. 2020;6(10):FSO664. DOI: 10.2144/fsoa-2020-0149.