Anesthetic and Perioperative Care: Improving Long-Term Outcomes

Educational Objectives

The goal of this program is to improve management of postsurgical complications associated with anesthesia. After hearing and assimilating this program, the clinician will be better able to:

1. Use continuous peripheral nerve catheters in amputation for pain.
2. Cite definitions of acute kidney disease as per Kidney Disease Improving Global Outcomes criteria.
3. Compare effects of hydroxyethyl starch vs crystalloids for fluid management in patients undergoing cystectomy.

Summary

Effect of anesthetics on cancer outcomes: Enlund et al (2014) reported ≈5% improved survival at 1 and 5 yr with propofol-based total intravenous anesthesia (TIVA) in patients with breast, colon, and rectal cancers; Wigmore et al (2016) found a 6.5% better survival at 1 yr and ≈5% at 5 yr in the propofol group than in the sevoflurane group; studies in the laboratory and on animals suggested a favorable effect of propofol in minimizing the adverse effects of apoptosis, proliferation, migration, and infiltration; a systematic review and meta-analysis of the studies found no difference in recurrence-free survival between volatile anesthetics and propofol; however, overall survival improves with propofol-based TIVA techniques; Enlund et al (2022) found no difference in recurrence-free survival between matched propofol and sevoflurane groups with breast cancer, but the propofol group had better overall survival at 5 yr; Cao et al (2023) performed a prospective randomized controlled trial (RCT) and reported no difference between the propofol and sevoflurane groups in overall survival for ≈3 yr; currently, there is no level 1 evidence to recommend one type of anesthetic technique over another to improve cancer outcomes

Regional anesthesia and persistent postsurgical pain: chronic postsurgical pain has various definitions; the most adopted definition is pain persisting ≥3 mo after surgery that was absent before surgery or has different characteristics or increased severity from preoperative pain and is localized to the surgical site, and all other possible causes of pain are excluded; persistent postsurgical pain incidence rate is very low for superficial cutaneous surgery; the incidence rates are >50% mostly in cases involving a neuropathic component, including amputation, thoracotomy, postmastectomy, inguinal hernia repair, open cholecystectomy, and cesarean delivery; incidence varies during the initial 90 days after the surgery; incidence of chronic postsurgical pain at 1 yr is 12%; ≈40% of all these patients have a neuropathic component; the single most important clinical factor that the anesthesiologists can use to minimize the risk is to adequately control the acute pain experience during the hospital stay, especially in the initial 24 to 48 hr

Breast postmastectomy model: has been the most studied; causes of postsurgical pain include pre-existing pain conditions and genetic predisposition based on psychosocial behavior factors (eg, anxiety, depression, catastrophizing, sleep disturbances, somatization, coping strategies); pathologic mechanisms involve interplay between the nociceptive activating mechanisms and antinociceptive mechanisms; there is an activation of nociceptive mechanisms in normal patients after surgery during the initial 48 to 72 hr; after 48 to 72 hr, antinociceptive mechanisms counter this activation to normalize patients; in patients at risk for chronic postsurgical pain, the antinociceptive mechanisms activate late during the recovery trajectory; in patients with pre-existing pain, the antinociceptive mechanisms have already been activated and depleted and are no longer available to counter surgical pain; Cochrane review (Weinstein et al [2018]) reported regional blocks were very effective in controlling postsurgical pain in thoracotomy, post-mastectomy, and cesarean delivery

Postamputation phantom limb: has a very high incidence and high neuropathic component; Ilfeld et al (2021) found patients with continuous peripheral nerve catheters placed for ≥4 days had significant improvement in their pain scores and clinically relevant pain relief compared with controls; the study also reported significant improvement in residual limb pain; Ilfeld et al (2023) reported no difference in the postamputation phantom limb pain and residual limb pain with ultrasonography-guided percutaneous cryoneurolysis 4 mo after treatment

Trials under way: The ROCKeT trial is evaluating ketamine for minimizing chronic postsurgical pain risk; PLAN trial and LOLIPOP trial are evaluating the role of intravenous lidocaine infusion on postmastectomy pain; the GAP study is evaluating the role of gabapentin in reducing cognitive complications with chronic postsurgical pain as a secondary outcome; another study is evaluating the role of dexmedetomidine in cognitive complications with chronic postsurgical pain as a secondary outcome

Management of patients with chronic postsurgical pain: identify patients with high risk for chronic postsurgical pain, provide counseling, avoid intraoperative nerve injury, and provide effective multimodal postoperative analgesia, especially in the initial 24 to 48 hr; regional analgesia may be beneficial in thoracotomy, mastectomy, patients undergoing cesarean delivery and those with postamputation pain conditions; the most important thing is to intervene early in high-risk patients; patients with pre-existing pain conditions, particularly fibromyalgia, patients with psychosocial behavioral factors with high risk for persistent postsurgical pain should receive transitional pain service early in treatment plan, if possible

Postoperative acute kidney injury (AKI): an often overlooked postoperative complication; may have significant long-term effects; a syndrome with multifactorial etiology and is most studied in vascular and cardiac patients; the published incidence varies from 20% to 70% depending on the definition, criteria and pre-existing patient risk factors; in patients undergoing nonvascular surgery, it is not as well studied; older literature suggested a rate from 5% to 60%; most recent studies suggested an AKI incidence of ≈15%; unresolved postoperative AKI is strongly associated with long-term complications and increased risk for death; postoperative AKI involves severity and duration

AKI categories: Kidney Disease Improving Global Outcomes (KDIGO) definition is most often used and is most widely accepted; KDIGO criteria includes assessment of drop in urine output and rise in serum creatinine; categorized into severity grade 1, 2, or 3; based on duration of rise in serum creatinine in postoperative period it is categorized as AKI (≤7 days), acute kidney disease (beyond 7 days to 90 days), and chronic kidney disease (CKD; >3 mo) based on the duration of rise of serum creatinine in the postoperative period; AKI could be transient (0-3 days) or persistent (3-7 days); patients with transient AKI that normalizes in ≤7 days most likely have no long-term complications; there is also less likelihood of long-term complications in persistent postoperative AKI if intervened early and normalizes before discharge

Possible reasons for AKI: frequently occurs in case of perioperative anemia, hypotension, inadequate volume resuscitation not intervened early, and use of intravenous contrast dyes for imaging or evaluating postoperative complications; there is a loss of 75% estimated glomerular filtration rate (eGFR) by the time the serum creatinine raises to 2 mg/dL; it is critical, especially in high-risk patients with major surgery, to check serum creatinine on postoperative day 1 and intervene early and rapidly if there is a trend of rising creatinine with low urine output; subclinical AKI is not detected by rise in serum creatinine; detected by biomarkers for cellular stress (eg, TIMP-2, IGFBP7) and cellular injury (eg, interleukin-18, kidney injury molecule-1); Hsu et al (2020) reported a hazard ratio (HR) of 2 for major adverse kidney events, defined as 25% reduction in eGFR, progression to CKD, long-term dialysis, or all-cause death, in patients with resolving AKI; patients with nonresolving AKI have a HR of 6

Prevention: there are modifiable and nonmodifiable preoperative risk factors; postoperative risk factors are often beyond the control of anesthesiologists as the surgeons in the United States do most of the postoperative care; postoperative factors include postoperative anemia, ventilatory strategies, especially in patients in intensive care unit (ICU) with poor lungs, abdominal compartment syndrome, thrombosis, postoperative nephrotoxins, and infectious complications

Minimizing oxygen debt: involves avoiding hypotension, maintaining cardiac output, avoiding severe anemia, fluid management, use of vasopressors perioperatively, colloids (starch and albumin), and crystalloids (saline and balanced salt solution); Salmasi et al (2017) reported an association of duration of hypotension with myocardial injury and AKI; there was no difference in the outcome between absolute hypotension (mean arterial pressure [MAP] <65 mm Hg) and <20% reduction from baseline; Mathis et al (2020) reported that patients with low baseline risk for postoperative kidney injury tolerate hypotension without any long-term adverse events, patients with moderate risk need to maintain a MAP >50 mm Hg, and patients with high risk need to maintain a MAP >60 mm Hg; in clinical practice, there is a reduction in intraoperative fluid administration and increase in vasopressor use for maintaining the MAP; Chiu et al (2022) reported a reduction in total crystalloid administered (mL/kg per hr) between 2015 and 2019; patients receiving less fluids along with vasopressors is increased and hypotension was avoided; however, the incidence of AKI was increased; maintaining MAP at the cost of inadequate fluid administration or not maintaining cardiac output is deleterious for all patients in terms of AKI and long-term complications

Preoperative anemia: there is less buffer for losing blood in patients with anemia to minimize AKI risk; study (Karkouti et al [2011]) reported a higher rise in serum creatinine in patients with anemia undergoing cardiac surgery who received erythrocytes vs nonanemic patients; managing preoperative anemia is important to reduce AKI and myocardial injury

Fluid management: there is a fear that administration of colloids, especially starch, in critically ill patients had an increased risk for major adverse events; however, patients undergoing surgery differ from critically ill patients; patients in the ICU receive larger amounts of volume resuscitation than healthy patients in the operating room; other confounding factors (eg, infection) also contribute to poor outcome; meta-analysis (Pensier et al [2022]) found no difference in the risk for AKI and abdominal complications between patients receiving hydroxyethyl starch (HES) and patients receiving crystalloids; however, there was a higher transfusion rate in the HES group; Duncan et al (2020) reported no difference in any of the biomarkers of kidney injury, coagulation parameters (platelet count, platelet function), or long-term mortality between HES and albumin; similarly, a study (Kammerer et al [2018]) reported no difference in AKI with HES and albumin in patients undergoing cystectomy at day 3 and day 90; Maheshwari et al (2020) reported no difference between saline and lactated Ringer’s solution in a composite outcome of in-hospital mortality and major complications; however, in secondary analysis, there was a statistically significant increase (but of nonmeaningful clinical relevance) in AKI in the saline group (with absolute difference of 0.4%); Chen et al (2023) found no difference in mortality or need for renal replacement therapy between balanced salt solutions and saline

Readings

Cao SJ, Zhang Y, Zhang YX, et al. Long-term survival in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: follow-up of a multicentre randomised trial. Br J Anaesth. 2023;131(2):266-275. doi:10.1016/j.bja.2023.01.023; Chen Y, Gao Y. Comparison of balanced crystalloids versus normal saline in critically ill patients: A systematic review with meta-analysis and trial sequential analysis of randomized controlled trials. Ther Clin Risk Manag. 2023;19:783-799. Published 2023 Oct 11. doi:10.2147/TCRM.S416785; Chiu C, Fong N, Lazzareschi D, et al. Fluids, vasopressors, and acute kidney injury after major abdominal surgery between 2015 and 2019: A multicentre retrospective analysis. Br J Anaesth. 2022;129(3):317-326. doi:10.1016/j.bja.2022.05.002; Duncan AE, Jia Y, Soltesz E, et al. Effect of 6% hydroxyethyl starch 130/0.4 on kidney and haemostatic function in cardiac surgical patients: A randomised controlled trial. Anaesthesia. 2020;75(9):1180-1190. doi:10.1111/anae.14994; Enlund M, Berglund A, Andreasson K, et al. The choice of anaesthetic--sevoflurane or propofol--and outcome from cancer surgery: A retrospective analysis. Ups J Med Sci. 2014;119(3):251-261. doi:10.3109/03009734.2014.922649; Enlund M, Berglund A, Enlund A, et al. Volatile versus propofol general anesthesia and long-term survival after breast cancer surgery: A National Registry Retrospective Cohort Study. Anesthesiology. 2022;137(3):315-326. doi:10.1097/ALN.0000000000004309; Hsu CY, Chinchilli VM, Coca S, et al. Post-acute kidney injury proteinuria and subsequent kidney disease progression: The assessment, serial evaluation, and subsequent sequelae in acute kidney injury (ASSESS-AKI) Study. JAMA Intern Med. 2020;180(3):402-410. doi:10.1001/jamainternmed.2019.6390; Ilfeld BM, Khatibi B, Maheshwari K, et al. Immediate effects of a continuous peripheral nerve block on postamputation phantom and residual limb pain: Secondary outcomes from a multicenter randomized controlled clinical trial. Anesth Analg. 2021;133(4):1019-1027. doi:10.1213/ANE.0000000000005673; Ilfeld BM, Smith CR, Turan A, et al. Ultrasound-guided percutaneous cryoneurolysis to treat chronic postamputation phantom limb pain: A multicenter randomized controlled trial. Anesthesiology. 2023;138(1):82-97. doi:10.1097/ALN.0000000000004429; Kammerer T, Brettner F, Hilferink S, et al. No Differences in renal function between balanced 6% hydroxyethyl starch (130/0.4) and 5% albumin for volume replacement therapy in patients undergoing cystectomy: A randomized controlled trial [published correction appears in Anesthesiology. 2018 Apr;128(4):863]. Anesthesiology. 2018;128(1):67-78. doi:10.1097/ALN.0000000000001927; Karkouti K, Wijeysundera DN, Yau TM, et al. The influence of erythrocyte transfusion on the risk of acute kidney injury after cardiac surgery differs in anemic and nonanemic patients. Anesthesiology. 2011;115(3):523-530. doi:10.1097/ALN.0b013e318229a7e8; Levey AS. Defining AKD: The Spectrum of AKI, AKD, and CKD. Nephron. 2022;146(3):302-305. doi: 10.1159/000516647. Epub 2021 Jun 24. PMID: 34167119; Mathis MR, Naik BI, Freundlich RE, et al. Preoperative risk and the association between hypotension and postoperative acute kidney injury [published correction appears in Anesthesiology. 2020 Jan 6;:]. Anesthesiology. 2020;132(3):461-475. doi:10.1097/ALN.0000000000003063; Pensier J, Deffontis L, Rollé A, et al. Hydroxyethyl starch for fluid management in patients undergoing major abdominal surgery: A systematic review with meta-analysis and trial sequential analysis [published correction appears in Anesth Analg. 2022 Sep 1;135(3):e20]. Anesth Analg. 2022;134(4):686-695. doi:10.1213/ANE.0000000000005803; Salmasi V, Maheshwari K, Yang D, et al. Relationship between intraoperative hypotension, defined by either reduction from baseline or absolute thresholds, and acute kidney and myocardial injury after noncardiac surgery: A retrospective cohort analysis. Anesthesiology. 2017;126(1):47-65. doi:10.1097/ALN.0000000000001432; Thapa P, Euasobhon P. Chronic postsurgical pain: Current evidence for prevention and management. Korean J Pain. 2018;31(3):155-173. doi:10.3344/kjp.2018.31.3.155; Weinstein EJ, Levene JL, Cohen MS, et al. Local anaesthetics and regional anaesthesia versus conventional analgesia for preventing persistent postoperative pain in adults and children. Cochrane Database Syst Rev. 2018;4(4):CD007105. Published 2018 Apr 25. doi:10.1002/14651858.CD007105.pub3; Wigmore TJ, Mohammed K, Jhanji S. Long-term survival for patients undergoing volatile versus IV anesthesia for cancer surgery: A retrospective analysis. Anesthesiology. 2016;124(1):69-79. doi:10.1097/ALN.0000000000000936; Maheshwari K, Turan A, Makarova N, et al. Saline versus Lactated Ringer's Solution: The Saline or Lactated Ringer's (SOLAR) Trial. Anesthesiology. 2020;132(4):614-624. doi:10.1097/ALN.0000000000003130.

Disclosures

For this program, the following relevant financial relationships were disclosed and mitigated to ensure that no commercial bias has been inserted into this content: Dr. Gottumukkala is a consultant for Masimo Corporation. Members of the planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Gottumukkala was recorded at the Texas Society of Anesthesiologists 2023 Annual Meeting, held September 7-10, 2023, in Round Rock, TX, and presented by the Texas Society of Anesthesiologists. For information on future CME activities from this presenter, please visit www.tsa.org. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.25 CE contact hours.

Lecture ID:

AN661702

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.