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Perioperative organ dysfunction: a burden to be countered

Definition and pathophysiology

In the perioperative setting, organ dysfunction is characterized as an inability of a given organ to perform its functions in a reversible or irreversible manner leading to altered homeostasis requiring clinical interventions or life support to maintain its normal physiology. The development of such complication leads to prolonged hospitalization, increased perioperative morbidity and mortality with short- and long-term consequences having a direct influence on the health-disease process of surgical patients.11 Marshall JC, Cook DJ, Christou NV, Bernard GR, Sprung CL, Sibbald WJ. Multiple Organ Dysfunction Score: A reliable descriptor of a complex clinical outcome. Crit Care Med. 1995;23: 1638–52., 22 Bartels K, Karhausen J, Clambey ET, Grenz A, Eltzschig HK. Perioperative Organ Injury. Anesthesiology. 2013;119:1474–89. Despite the decrease in anesthesia-related deaths in recent times,33 Bainbridge D, Martin J, Arango M, Cheng D. Perioperative and anaesthetic-related mortality in developed and developing countries: a systematic review and meta-analysis. Lancet (London, England). 2012;380:1075–81. deaths related to organ dysfunction in the perioperative period are among the four main causes of death, if they are epidemio-logically considered according to the categories reported by the Center for Disease Control. This important clinical issue is ranked just behind cardiovascular diseases, cancer-related deaths and cerebrovascular diseases according to a study published in the American Society of Anesthesiologists (ASA) journal (2). Therefore, the correct identification of patients, who are at higher risk to develop any organ malfunction throughout the perioperative period, is crucial to deliver proper anesthesia care targeting organ protection for better clinical outcomes.

The molecular mechanism of the development of a surgery-related organ dysfunction perioperatively is not completely elucidated. However, pathophysiologically, one of the postulated mechanisms is that its origin could be directly related to uncontrolled inflammation, either of infectious focus like microbial-associated molecular patterns (MAMPs, expressed by pathogens) progressing to sepsis,44 Seymour CW, Kennedy JN, Wang S, et al. Derivation, Validation, and Potential Treatment Implications of Novel Clinical Pheno-types for Sepsis. JAMA. 2019;321:2003–17. or a systemic inflammatory syndrome (SIRS) due to excessive production of damage-associated molecular patterns (DAMPS).55 Margraf A, Ludwig N, ZarbockA, Rossaint J. Systemic Inflammatory Response Syndrome After Surgery: Mechanisms and Protection. Anesth Analg. 2020;131:1693–707. Both pathways activate immune mechanisms mediated by Toll-like receptors (TLRs), major pattern recognition receptors (PRRs), releasing diverse pro-inflammatory cytokines, chemokines, interferons and reactive oxygen, and nitrogen species, propagating uncontrolled systemic inflammation in individuals genetically prone. This uninhibited inflammation will result in vascular damage, endothelial dysfunction, tissue malperfusion, mitochondrial dysfunction and as a final consequence irreversible cell damage leading to organ dysfunction.55 Margraf A, Ludwig N, ZarbockA, Rossaint J. Systemic Inflammatory Response Syndrome After Surgery: Mechanisms and Protection. Anesth Analg. 2020;131:1693–707. The most frequent surgery-related organ dysfunctions are summarized in Figure 1.

Figure 1
The most frequent organ dysfunctions encountered in the perioperative period. * non-ARDS lung injury, prolonged need for supplemental oxygen, atelectasis, pleural effusion, pneumonia, and reintubation; ARDS, severe acute respiratory syndrome; MINS, myocardial injury after noncardiac surgery; POD, postoperative delirium; POCD, postoperative cognitive dysfunction; POAF, postoperative atrial fibrillation. All images were created with BioRender.com by Ricardo Esper Treml using Academic License Terms.

Brazilian scenario

The Brazilian epidemiology of perioperative mortality resembles the international trend of developed and non-developed countries.33 Bainbridge D, Martin J, Arango M, Cheng D. Perioperative and anaesthetic-related mortality in developed and developing countries: a systematic review and meta-analysis. Lancet (London, England). 2012;380:1075–81. Since 2008 with the first epidemiological study66 Lobo SM, Rezende E, Knibel MF, et al. Epidemiology and outcomes of non-cardiac surgical patients in Brazilian intensive care units. Rev Bras Ter Intensiva. 2008;20:376–84. in high-risk patients evaluating the development of perioperative complications in non-cardiac surgery, the Brasis study77 Silva Júnior JM, Chaves RCF, Corrêa TD, et al. Epidemiology and outcome of high-surgical-risk patients admitted to an intensive care unit in Brazil. Rev Bras Ter Intensiva. 2020;32:17–27. in 2020, a significant reduction in mortality has been showed, although they assess different perioperative mortality endpoints (Fig. 2). This reduction may reflect the introduction of new protocols of multidisciplinary multimodal perioperative care optimization which aimed to establish improvements in perioperative care in Brazil.88 JE DE-A-N, SalomÃo AB, Caporossi C, et al. ACERTO Project - 15 years changing perioperative care in Brazil. Rev Col Bras Cir. 2021;48:e20202832. However, when the incidence of the composite of postoperative complications is analyzed, a marginal progress can be seen in reducing major perioperative complications, which are mainly surgery-related organ dysfunctions. This fact is comparable to the international literature, especially American and European, in which during the past years it has also slowly decreased.22 Bartels K, Karhausen J, Clambey ET, Grenz A, Eltzschig HK. Perioperative Organ Injury. Anesthesiology. 2013;119:1474–89., 99 Yip W, Ghoreifi A, Gerald T, et al. Perioperative Complications and Oncologic Outcomes of Nephrectomy Following Immune Checkpoint Inhibitor Therapy: A Multicenter Collaborative Study. Eur Urol Oncol. 2023. https://doi.org/10.1016/j.euo.2023.03.003. Online ahead of print.
https://doi.org/10.1016/j.euo.2023.03.00...
, 1010 POSE-Study group. Peri-interventional outcome study in the elderly in Europe: A 30-day prospective cohort study. Eur J Anaesthesiol. 2022;39:198–209. The main organ dysfunctions in both Brazilian studies were cardiovascular, followed by neurological and renal. Abdominal surgery accounted for the highest incidence of complications in both studies. Some independent risk factors were advanced age, emergency and urgent surgery, preoperative anemia, intraoperative transfusion, higher intraoperative fluid balance and high preoperative sequential organ failure assessment score (SOFA) and simplified acute physiology score (SAPS) scores.66 Lobo SM, Rezende E, Knibel MF, et al. Epidemiology and outcomes of non-cardiac surgical patients in Brazilian intensive care units. Rev Bras Ter Intensiva. 2008;20:376–84., 77 Silva Júnior JM, Chaves RCF, Corrêa TD, et al. Epidemiology and outcome of high-surgical-risk patients admitted to an intensive care unit in Brazil. Rev Bras Ter Intensiva. 2020;32:17–27., 1111 Gomes BC, Lobo SMA, Sá Malbouisson LM, et al. Trends in perioperative practices of high-risk surgical patients over a 10-year interval. PLoSOne. 2023;18:e0286385. Interestingly, even in low-risk patients, perioperative complications were present in significant numbers, with cardiovascular dysfunction accounting for 5.3% of them. This shows the importance of surveillance and preventive efforts even in this low-risk patient population. Nonetheless, some methodological points of these studies limit generalization of the data for the entire country and for all profiles of patients undergoing different surgeries in Brazil.

Figure 2
Dynamics of Brazilian epidemiology regarding mortality and incidence of perioperative complications. EMAPO, Multicenter study of perioperative evaluation for non-cardiac surgeries in Brazil (EMAPO);1414 Pinho C, Grandini PC, Gualandro DM, Calderaro D, Monachini M, Caramelli B. Multicenter study of perioperative evaluation for noncardiac surgeries in Brazil (EMAPO). Clinics (Sao Paulo, Brazil). 2007;62:17–22. Brasis: Epidemiology and outcome of high-surgical-risk patients admitted to an intensive care unit in Brazil.1515 Silva-Jr JM, Menezes PFL, Lobo SM, et al. Impact of perioperative hemodynamic optimization therapies in surgical patients: economic study and meta-analysis. BMC Anesthesiol. 2020;20:71. All images were created with BioRender.com by Ricardo Esper Treml using Academic License Terms.

First, geographically, more than half of the derived data from these studies are from southwest and south regions, hence, making the correct evaluation and comparison between central, north, and northwest regions difficult. Second, the core of the data comes from high-risk patients in non-cardiac surgeries, which makes a general assessment difficult in other populations such as cardiac surgery, pediatrics, and obstetric surgery. Ultimately, a direct evaluation and comparison of incidences in the Brazilian private and public sectors is necessary and has not been directly questioned in these studies. Regarding cardiac surgery and peri-operative organ dysfunction, a recently published multicenter prospective observational study by Palomba et al has shown in patients receiving coronary artery bypass graft surgery (CABG) under cardiopulmonary bypass a high incidence of cardiac surgery-associated acute kidney injury (CSA-AKI) in both studied groups. Moreover, this study also showed that fluid overload intraoperatively is associated with increased risk in hospital mortality and cardiovascular complications.1212 Palomba H, Treml RE, Caldonazo T, et al. Intraoperative fluid balance and cardiac surgery-associated acute kidney injury: a multicenter prospective study. Braz J Anesthesiol. 2022;72:688–94. A more comprehensive view at the incidence of organ dysfunction in other types of cardiac surgery and its associations with clinical outcomes is needed to better understand the Brazilian scenario in this specialty.

Impact of surgery-related organ dysfunction in clinical outcomes

As previously mentioned, the development of any organ dysfunction during the perioperative period is directly associated with worse clinical outcomes translated as prolonged stay in the intensive care unit and hospital, higher risk of surgical infection, and increased mortality.1313 Thiele RH, Theodore DJ, Gan TJ. Outcome of organ dysfunction in the perioperative period. Anesth Analg. 2021;133:393–405. The relationship between outcome and organ dysfunction varies greatly depending on the type of malfunction and surgery assessed. One example is the increased risk of death by 1.6 in patients undergoing hip surgery, with the development of postoperative delirium (POD).1313 Thiele RH, Theodore DJ, Gan TJ. Outcome of organ dysfunction in the perioperative period. Anesth Analg. 2021;133:393–405. In addition, the development of myocardial injury after noncardiac surgery (MINS) is strongly associated with 30-day mortality.1313 Thiele RH, Theodore DJ, Gan TJ. Outcome of organ dysfunction in the perioperative period. Anesth Analg. 2021;133:393–405. Even simple hyperglycemia is related to increased risk of infections and perioperative mortality.11 Marshall JC, Cook DJ, Christou NV, Bernard GR, Sprung CL, Sibbald WJ. Multiple Organ Dysfunction Score: A reliable descriptor of a complex clinical outcome. Crit Care Med. 1995;23: 1638–52.,1313 Thiele RH, Theodore DJ, Gan TJ. Outcome of organ dysfunction in the perioperative period. Anesth Analg. 2021;133:393–405. Therefore, taking all these points into consideration, constant vigilance during the perioperative period is of paramount importance. Starting from the detection of patients at risk of developing surgery-related organ dysfunction in the preoperative period, as well as anesthesia planning and implementation of this intraoperatively, to optimization of therapy care postoperatively, the central point is the integral and complete transfer of the patient’s clinical information to ensure the absence of gaps in the delivery of clinical treatment. To achieve this, a multimodal and multidisciplinary approach involving all specialties related to the case is essential to deliver the best patient centered anesthesia care.

References

  • 1
    Marshall JC, Cook DJ, Christou NV, Bernard GR, Sprung CL, Sibbald WJ. Multiple Organ Dysfunction Score: A reliable descriptor of a complex clinical outcome. Crit Care Med. 1995;23: 1638–52.
  • 2
    Bartels K, Karhausen J, Clambey ET, Grenz A, Eltzschig HK. Perioperative Organ Injury. Anesthesiology. 2013;119:1474–89.
  • 3
    Bainbridge D, Martin J, Arango M, Cheng D. Perioperative and anaesthetic-related mortality in developed and developing countries: a systematic review and meta-analysis. Lancet (London, England). 2012;380:1075–81.
  • 4
    Seymour CW, Kennedy JN, Wang S, et al. Derivation, Validation, and Potential Treatment Implications of Novel Clinical Pheno-types for Sepsis. JAMA. 2019;321:2003–17.
  • 5
    Margraf A, Ludwig N, ZarbockA, Rossaint J. Systemic Inflammatory Response Syndrome After Surgery: Mechanisms and Protection. Anesth Analg. 2020;131:1693–707.
  • 6
    Lobo SM, Rezende E, Knibel MF, et al. Epidemiology and outcomes of non-cardiac surgical patients in Brazilian intensive care units. Rev Bras Ter Intensiva. 2008;20:376–84.
  • 7
    Silva Júnior JM, Chaves RCF, Corrêa TD, et al. Epidemiology and outcome of high-surgical-risk patients admitted to an intensive care unit in Brazil. Rev Bras Ter Intensiva. 2020;32:17–27.
  • 8
    JE DE-A-N, SalomÃo AB, Caporossi C, et al. ACERTO Project - 15 years changing perioperative care in Brazil. Rev Col Bras Cir. 2021;48:e20202832.
  • 9
    Yip W, Ghoreifi A, Gerald T, et al. Perioperative Complications and Oncologic Outcomes of Nephrectomy Following Immune Checkpoint Inhibitor Therapy: A Multicenter Collaborative Study. Eur Urol Oncol. 2023. https://doi.org/10.1016/j.euo.2023.03.003 Online ahead of print.
    » https://doi.org/10.1016/j.euo.2023.03.003
  • 10
    POSE-Study group. Peri-interventional outcome study in the elderly in Europe: A 30-day prospective cohort study. Eur J Anaesthesiol. 2022;39:198–209.
  • 11
    Gomes BC, Lobo SMA, Sá Malbouisson LM, et al. Trends in perioperative practices of high-risk surgical patients over a 10-year interval. PLoSOne. 2023;18:e0286385.
  • 12
    Palomba H, Treml RE, Caldonazo T, et al. Intraoperative fluid balance and cardiac surgery-associated acute kidney injury: a multicenter prospective study. Braz J Anesthesiol. 2022;72:688–94.
  • 13
    Thiele RH, Theodore DJ, Gan TJ. Outcome of organ dysfunction in the perioperative period. Anesth Analg. 2021;133:393–405.
  • 14
    Pinho C, Grandini PC, Gualandro DM, Calderaro D, Monachini M, Caramelli B. Multicenter study of perioperative evaluation for noncardiac surgeries in Brazil (EMAPO). Clinics (Sao Paulo, Brazil). 2007;62:17–22.
  • 15
    Silva-Jr JM, Menezes PFL, Lobo SM, et al. Impact of perioperative hemodynamic optimization therapies in surgical patients: economic study and meta-analysis. BMC Anesthesiol. 2020;20:71.

Publication Dates

  • Publication in this collection
    22 Apr 2024
  • Date of issue
    2024

History

  • Received
    30 Jan 2024
  • Accepted
    30 Jan 2024
  • Published
    30 Jan 2024
Sociedade Brasileira de Anestesiologia (SBA) Rua Professor Alfredo Gomes, 36, Botafogo , cep: 22251-080 - Rio de Janeiro - RJ / Brasil , tel: +55 (21) 97977-0024 - Rio de Janeiro - RJ - Brazil
E-mail: editor.bjan@sbahq.org