Skip to main content
SpringerLink
Log in

An Analysis of Anesthesia Induction Dosing in Female Older Adults

  • Original Research Article
  • Published:
Drugs & Aging Aims and scope Submit manuscript

Abstract

Background/Objectives

In the context of an aging surgical population, appropriate anesthetic induction dose adjustments for the older adult remain poorly defined. In the present study, we describe the prevalence of excess induction agent dose in reference to US Food and Drug Administration (FDA) guidance and seek to investigate the possible association of such excess dose with postinduction hypotension and postoperative acute kidney injury (AKI).

Study Design

A retrospective observational study was conducted in a large tertiary teaching hospital in accordance with our a priori analytic protocol as registered on ClinicalTrials.gov (NCT03699696). For inclusion, patients had to be 65 years or older and to have received general anesthesia with propofol induction for gynecologic oncology surgery between December 1, 2014 and July 8, 2018. Descriptive variables of the patients, machine-captured perioperative vital signs, induction anesthetic, and vasopressor/inotrope administrations were recorded.

Main Outcome Measures

A total of 541 female patients met inclusion criteria. The mean (standard deviation) age of the cohort was 72.20 (5.93) years. Regarding the primary outcome, 65.43% (354 patients, 95% confidence interval 61.2–69.4) of the cohort received more than the FDA recommended 1–1.5 mg/kg induction dose for patients of advanced age undergoing general anesthesia.

Results

The percentage of patients receiving doses in excess of the FDA guidance remained substantial across all age groups, but decreased progressively with increasing 5-year age intervals (from 74% among those aged 65–69 years to 44% among those aged > 80 years). Excess propofol dose in the present cohort was not associated with our a priori definition of postinduction hypotension. Regarding AKI, among the 30 patients suffering this outcome, it occurred less often in patients who received higher propofol doses (4.1% [9/217] vs. 15.3% [21/138], p < 0.001), a result that may have been confounded by differential rates of missingness.

Conclusions

Older adults commonly receive propofol induction doses in excess of the FDA guidance. The immediate hemodynamic effects of these doses on postinduction hypotension were not seen in the present cohort, suggesting that propofol dose adjustments may serve as a marker of physicians’ judgments as to the frailty of patients. The relevance of the AKI association is difficult to interpret due to the non-differential missingness of AKI data between the two groups.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Bureau USC. Older people projected to outnumber children for first time in U.S. history. September 6, 2018 [cited August 8, 2019]. https://www.census.gov/newsroom/press-releases/2018/cb18-41-population-projections.html. Accessed 8 Aug 2019.

  2. Mangoni AA, Jackson SH. Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications. Br J Clin Pharmacol. 2004;57(1):6–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. White SM. Including the very elderly in clinical trials. Anaesthesia. 2010;65(8):778–80.

    Article  CAS  PubMed  Google Scholar 

  4. Strøm C, Rasmussen LS, Sieber FE. Should general anaesthesia be avoided in the elderly? Anaesthesia. 2014;69(Suppl 1):35–44.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Hedman AM, van Haren NEM, Schnack HG, Kahn RS, Pol HEH. Human brain changes across the life span: a review of 56 longitudinal magnetic resonance imaging studies. Hum Brain Mapp. 2012;33(8):1987–2002.

    Article  PubMed  Google Scholar 

  6. Zeevi N, Pachter J, McCullough LD, Wolfson L, Kuchel GA. The blood-brain barrier: geriatric relevance of a critical brain-body interface. J Am Geriatr Soc. 2010;58(9):1749–57.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Couillard-Despres S, Iglseder B, Aigner L. Neurogenesis, cellular plasticity and cognition: the impact of stem cells in the adult and aging brain—a mini-review. Gerontology. 2011;57(6):559–64.

    Article  PubMed  Google Scholar 

  8. Ownby RL. Neuroinflammation and cognitive aging. Curr Psychiatry Rep. 2010;12(1):39–45.

    Article  PubMed  Google Scholar 

  9. Ekstein M, Gavish D, Ezri T, Weinbroum AA. Monitored anaesthesia care in the elderly—guidelines and recommendations. Drugs Aging. 2008;25(6):477–500.

    Article  CAS  PubMed  Google Scholar 

  10. Schnider TW, Minto CF, Shafer SL, Gambus PL, Andresen C, Goodale DB, et al. The influence of age on propofol pharmacodynamics. Anesthesiology. 1999;90(6):1502–16.

    Article  CAS  PubMed  Google Scholar 

  11. FDA. DIPRIVAN. April 2017 [cited August 13, 2019]; https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019627s066lbl.pdf. Accessed 13 Aug 2019.

  12. Kazama T, Ikeda K, Morita K, Kikura M, Doi M, Ikeda T, et al. Comparison of the effect-site k(eO)s of propofol for blood pressure and EEG bispectral index in elderly and younger patients. Anesthesiology. 1999 Jun;90(6):1517-27.

  13. Cressey DM, Claydon P, Bhaskaran NC, Reilly CS. Effect of midazolam pretreatment on induction dose requirements of propofol in combination with fentanyl in younger and older adults. Anaesthesia. 2001;56(2):108–13.

    Article  CAS  PubMed  Google Scholar 

  14. Abelha FJ, Botelho M, Fernandes V, Barros H. Determinants of postoperative acute kidney injury. Critical Care. 2009;13(3):R79.

    Article  Google Scholar 

  15. Kheterpal S, Tremper KK, Heung M, Rosenberg AL, Englesbe M, Shanks AM, et al. Development and validation of an acute kidney injury risk index for patients undergoing general surgery. Anesthesiology. 2009;110(3):505–15.

    Article  PubMed  Google Scholar 

  16. Walsh M, Devereaux PJ, Garg AX, Kurz A, Turan A, Rodseth RN, et al. Relationship between intraoperative mean arterial pressure and clinical outcomes after noncardiac surgery: toward an empirical definition of hypotension. Anesthesiology. 2013;119(3):507–15.

    Article  PubMed  Google Scholar 

  17. Sun LY, Wijeysundera DN, Tait GA, Beattie WS. Association of Intraoperative hypotension with acute kidney injury after elective noncardiac surgery. Anesthesiology. 2015;123(3):515–23.

    Article  PubMed  Google Scholar 

  18. Kheterpal S, Tremper KK, Englesbe MJ, O’Reilly M, Shanks AM, Fetterman DM, et al. Predictors of postoperative acute renal failure after noncardiac surgery in patients with previously normal renal function. Anesthesiology. 2007;107(6):892–902.

    Article  PubMed  Google Scholar 

  19. Brienza N, Giglio MT, Marucci M, Fiore T. Does perioperative hemodynamic optimization protect renal function in surgical patients? A meta-analytic study. Critical Care Medicine. 2009;37(6):2079–90.

    Article  PubMed  Google Scholar 

  20. Lee LO, Bateman BT, Kheterpal S, Klumpner TT, Housey M, Aziz MF, et al. Risk of epidural hematoma after neuraxial techniques in thrombocytopenic parturients: a report from the Multicenter Perioperative Outcomes Group. Anesthesiology. 2017;126(6):1053–63.

    Article  PubMed  PubMed Central  Google Scholar 

  21. de Graaff JC, Pasma W, van Buuren S, Duijghuisen JJ, Nafiu OO, Kheterpal S, et al. Reference values for noninvasive blood pressure in children during anesthesia: a multicentered retrospective observational cohort study. Anesthesiology. 2016;125(5):904–13.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Berman MF, Iyer N, Freudzon L, Wang S, Freundlich RE, Housey M, et al. Alarm limits for intraoperative drug infusions: a report from the Multicenter Perioperative Outcomes Group. Anesth Analg. 2017;125(4):1203–11.

    Article  PubMed  Google Scholar 

  23. Aziz MF, Brambrink AM, Healy DW, Willett AW, Shanks A, Tremper T, et al. Success of intubation rescue techniques after failed direct laryngoscopy in adults: a retrospective comparative analysis from the Multicenter Perioperative Outcomes Group. Anesthesiology. 2016;125(4):656–66.

    Article  PubMed  Google Scholar 

  24. Bateman BT, Mhyre JM, Ehrenfeld J, Kheterpal S, Abbey KR, Argalious M, et al. The risk and outcomes of epidural hematomas after perioperative and obstetric epidural catheterization: a report from the Multicenter Perioperative Outcomes Group Research Consortium. Anesth Analg. 2013;116(6):1380–5.

    Article  PubMed  Google Scholar 

  25. Kheterpal S, Healy D, Aziz MF, Shanks AM, Freundlich RE, Linton F, et al. Incidence, predictors, and outcome of difficult mask ventilation combined with difficult laryngoscopy: a report from the multicenter perioperative outcomes group. Anesthesiology. 2013;119(6):1360–9.

    Article  PubMed  Google Scholar 

  26. Bender SP, Paganelli WC, Gerety LP, Tharp WG, Shanks AM, Housey M, et al. Intraoperative lung-protective ventilation trends and practice patterns: a report from the Multicenter Perioperative Outcomes Group. Anesth Analg. 2015;121(5):1231–9.

    Article  PubMed  Google Scholar 

  27. Sun E, Mello MM, Rishel CA, Vaughn MT, Kheterpal S, Saager L, et al. Association of overlapping surgery with perioperative outcomes. JAMA. 2019;321(8):762–72.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Kheterpal S. Clinical research using an information system: the multicenter perioperative outcomes group. Anesthesiol Clin. 2011;29(3):377–88.

    Article  PubMed  Google Scholar 

  29. Dripps RD, Lamont A, Eckenhoff JE. The role of anesthesia in surgical mortality. JAMA. 1961;178(3):261–6.

    Article  CAS  PubMed  Google Scholar 

  30. Schonberger RB, Dutton RP, Dai F. Is there evidence for systematic upcoding of ASA physical status coincident with payer incentives? A regression discontinuity analysis of the National Anesthesia Clinical Outcomes Registry. Anesth Analg. 2016;122(1):243–50.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Quan H, Sundararajan V, Halfon P, Fong A, Burnand B, Luthi JC, et al. Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care. 2005;43(11):1130–9.

    Article  PubMed  Google Scholar 

  32. van Walraven C, Austin PC, Jennings A, Quan H, Forster AJ. A modification of the Elixhauser comorbidity measures into a point system for hospital death using administrative data. Med Care. 2009;47(6):626–33.

    Article  PubMed  Google Scholar 

  33. Elixhauser A, Steiner C, Harris DR, Coffey RM. Comorbidity measures for use with administrative data. Med Care. 1998;36(1):8–27.

    Article  CAS  PubMed  Google Scholar 

  34. Rivera R, Antognini JF. Perioperative drug therapy in elderly patients. Anesthesiology. 2009;110(5):1176–81.

    Article  PubMed  Google Scholar 

  35. Jilek J, Fukushima T. Oscillometric blood pressure measurement: the methodology, some observations, and suggestions. Biomed Instrum Technol. 2005;39(3):237–41.

    PubMed  Google Scholar 

  36. Futier E, Lefrant JY, Guinot PG, Godet T, Lorne E, Cuvillon P, et al. Effect of individualized vs standard blood pressure management strategies on postoperative organ dysfunction among high-risk patients undergoing major surgery: a randomized clinical trial. JAMA. 2017;318(14):1346–57.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Salmasi V, Maheshwari K, Yang D, Mascha EJ, Singh A, Sessler DI, 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.

    Article  PubMed  Google Scholar 

  38. Vernooij LM, van Klei WA, Machina M, Pasma W, Beattie WS, Peelen LM. Different methods of modelling intraoperative hypotension and their association with postoperative complications in patients undergoing non-cardiac surgery. Br J Anaesth. 2018;120(5):1080–9.

    Article  CAS  PubMed  Google Scholar 

  39. Wu X, Jiang Z, Ying J, Han Y, Chen Z. Optimal blood pressure decreases acute kidney injury after gastrointestinal surgery in elderly hypertensive patients: a randomized study: Optimal blood pressure reduces acute kidney injury. J Clin Anesth. 2017;43:77–83.

    Article  PubMed  Google Scholar 

  40. Wesselink EM, Kappen TH, Torn HM, Slooter AJC, van Klei WA. Intraoperative hypotension and the risk of postoperative adverse outcomes: a systematic review. Br J Anaesth. 2018;121(4):706–21.

    Article  CAS  PubMed  Google Scholar 

  41. Monk TG, Bronsert MR, Henderson WG, Mangione MP, Sum-Ping ST, Bentt DR, et al. Association between intraoperative hypotension and hypertension and 30-day postoperative mortality in noncardiac surgery. Anesthesiology. 2015;123(2):307–19.

    Article  PubMed  Google Scholar 

  42. KDIGO. KDIGO clinical practice guideline for acute kidney injury. Kidney International Supplements. 2012;17:1-138.

  43. Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11(2):R31.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P. Acute renal failure—definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004;8(4):R204–12.

    Article  PubMed  PubMed Central  Google Scholar 

  45. MPOG. AKI 01. https://mpog.org/files/quality/measures/AKI-01_spec.pdf. August 13, 2019 [cited August 13, 2019]; Available from: https://mpog.org/files/quality/measures/AKI-01_spec.pdf. Accessed 13 Aug 2019.

  46. Akhtar S, Liu J, Heng J, Dai F, Schonberger RB, Burg MM. Does intravenous induction dosing among patients undergoing gastrointestinal surgical procedures follow current recommendations: a study of contemporary practice. J Clin Anesth. 2016;33:208–15.

    Article  PubMed  Google Scholar 

  47. Akhtar S, Heng J, Dai F, Schonberger RB, Burg MM. A retrospective observational study of anesthetic induction dosing practices in female elderly surgical patients: are we overdosing older patients? Drugs Aging. 2016;33(10):737–46.

    Article  CAS  PubMed  Google Scholar 

  48. Phillips AT, Deiner S, Mo Lin H, Andreopoulos E, Silverstein J, Levin MA. Propofol use in the elderly population: prevalence of overdose and association with 30-day mortality. Clin Ther. 2015;37(12):2676–85.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Chen EY, Sukumar N, Dai F, Akhtar S, Schonberger RB. A pilot analysis of the association between types of monitored anesthesia care drugs and outcomes in transfemoral aortic valve replacement performed without general anesthesia. J Cardiothorac Vasc Anesth. 2018;32(2):666–71.

    Article  PubMed  Google Scholar 

  50. Schonberger RB, Gilbertsen T, Dai F. The problem of controlling for imperfectly measured confounders on dissimilar populations: a database simulation study. J Cardiothorac Vasc Anesth. 2014;28(2):247–54.

    Article  PubMed  Google Scholar 

  51. Ingrande J, Brodsky JB, Lemmens HJ. Lean body weight scalar for the anesthetic induction dose of propofol in morbidly obese subjects. Anesth Analg. 2011;113(1):57–62.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health (NIH) or the United States government.

Author information

Authors and Affiliations

  1. Department of Anesthesiology, Yale School of Medicine, 789 Howard Avenue, New Haven, CT, USA, 06519

    Eric Y. Chen, Shamsuddin Akhtar & Robert B. Schonberger

  2. Yale Center for Analytical Sciences, Yale School of Public Health, 300 George Street, Suite 555, New Haven, CT, USA, 06510

    Bin Zhou & Feng Dai

  3. Center For Medical Informatics, Yale School of Medicine, 300 George Street, Suite 501, New Haven, CT, USA, 06510

    George Michel

Authors
  1. Eric Y. Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. George Michel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bin Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Feng Dai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shamsuddin Akhtar
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Robert B. Schonberger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eric Y. Chen.

Ethics declarations

Conflict of interest

Dr. Schonberger holds an equity stake in Johnson & Johnson, a publicly traded, diversified manufacturer of healthcare products. The remaining authors, Eric Y. Chen, George Michel, Bin Zhou, Feng Dai, and Shamsuddin Akhtar, declare that they have no conflict of interest.

Consent to participate

For this type of study, formal consent was not required.

Funding

This work was supported in part by grant R01 AG059607 from the National Institute on Aging, as well as CTSA Grant Number UL1RR024139 from the National Center for Research Resources and the National Center for Advancing Translational Science, components of the NIH.

Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, E.Y., Michel, G., Zhou, B. et al. An Analysis of Anesthesia Induction Dosing in Female Older Adults. Drugs Aging 37, 435–446 (2020). https://doi.org/10.1007/s40266-020-00760-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40266-020-00760-3

Search

Navigation