Surgical stress response depends on perioperative care
The metabolic stress response varies widely. It seems to be commensurate with the extent and the type of the surgical procedure (Fig. 36.1). Surgical surrogate parameters such as operation time and blood loss have an important impact, and surgical stress is reduced by a minimally invasive approach. On the other hand, patient-related factors are important; risk factors are a diagnosis of cancer, concomitant malnutrition, and frailty with multiple comorbidities [6, 13, 21, 27]. A prolonged or excessive stress response inevitably leads to hypercatabolism and its feared sequelae – namely, hyperglycemia, immunosuppression, and depletion of muscle protein stores with consecutive hypoproteinemia. Clinical consequences are, among others, fatigue, pulmonary complications, wound healing problems, and ileus. Aiming for the prevention or early treatment of a pathological stress response is therefore mandatory [4, 21, 31, 53].
Several perioperative measures have been shown to dampen the excessive stress response, to restore homeostasis, and thus to positively influence clinical outcomes [22, 28]. These various interventions are addressed and discussed in the following paragraphs of this book chapter.
Obviously, reliable prediction of surgical stress response could help to guide the use of potential preventive or therapeutic interventions. The ideal marker or tool should be easy to use, available early, and inexpensive. To be meaningful, the marker needs to show a strong correlation with the extent of surgical trauma and with clinical outcome.
Insulin resistance has been proposed as a promising surrogate parameter for the extent of the postsurgical stress response [46, 47]. However, insulin resistance, as well as interleukin (IL)-6 and IL-10, have never found their way into routine clinical used because of sophisticated analysis techniques and cost issues. C-reactive protein (CRP) is used in clinical practice to document postoperative inflammation and to detect postoperative complications [1, 22, 40]. CRP peaks typically around postoperative day 2 or 3, which is too late to initiate measures to modulate the postoperative stress response.
Because no reliable predictor has yet been identified, combined measures should be applied to prevent a pathological stress response with deleterious consequences.
36.2 Postoperative Morbidity: Incidence, Risk Factors, Consequences
Despite evolving surgical techniques and increasing specialization, the occurrence of surgical complications seems to be unchanged. There is no doubt that surgical progress has been, to a certain extent, counteracted by extended indications and increasingly frail patients. On the other hand, the underlying pathophysiology of the postsurgical metabolic stress response was neglected for a long time by the surgical community. As a consequence, preventive measures are not yet widely implemented [7, 29]. Outcomes after colorectal surgery vary widely, and comparisons between studies are clearly hampered by serious methodological shortcomings such as different definitions, incomplete reporting, and heterogenous cohorts [15, 41, 52].
Three major randomized studies comparing open with laparoscopic procedures (the CLASSIC, COLOR, and COST trials) reported overall complication rates between 20 % and 33 % and median postoperative hospital stays from 5 to 11 days [11, 18, 48]. Outcomes were similar for open versus minimally invasive surgeries but slightly worse for rectal resections when compared with colectomies. Of note, none of the study protocols included enhanced recovery elements. The mortality rate was 1–2 % in the COST and COLOR studies and 4–5 % in the CLASSIC trial. However, true morbidity and mortality rates in the “real world” outside randomized trials are probably much higher and tend to increase considerably with longer follow-up: a recent nationwide study in England revealed 90 day mortality rates after colorectal surgery of 11.3 % . Complications are clearly related to longer hospital stay and increased level of care needed after discharge. Last, complications are associated with higher in-hospital mortality and to a delay in adjuvant treatment that leads to worse oncological outcomes [43, 44].
Multiple risk factors for postoperative complications were recently identified (Table 36.1). These include patient-related parameters such as age, male sex, higher ASA class, and obesity. A number of factors relate to the procedure and the surgeon (blood loss, operating time, experience). Most of these risk factors cannot be changed, but some of them are modifiable and thus offer opportunities for therapeutic interventions .
Pathological stress response: risk factors, prevention, and treatment
Type of surgery
Minimally invasive surgery
Consider preemptive conversion
Handle tissue gently
Nutritional screening and support
Early food intake
Smoking cessation counseling
Early food intake
Zero fluid balance
Early oral intake
Early discontinuation of intravenous fluids
Minimally invasive surgery
Stringent fluid administration
Opioid-sparing pain strategy
Omission of drains, nasogastric tubes
Early removal of Foley catheters
Recent improvements in perioperative care have targeted these modifiable risk factors and aim to modify a pathologically increased stress response. The resulting interventions and clinical pathways have been proven effective and are therefore outlined in the following sections (Table 36.1).
36.3 Optimizing Perioperative Management
36.3.1 Preparation: Smoking Cessation, Prehabilitation
The importance of initiation of protective measures before the offending hit (e.g., surgery) is largely acknowledged. Smoking is a modifiable risk factor that is particularely prone to pulmonary and wound-healing complications. An extensive recent Cochrane review summarized the findings from 13 randomized controlled trials (RCTs) including 2,010 patients . Using dedicated preoperative smoking cessation counseling with or without concomittant pharmacotherapy, postoperative complications could be reduced from 46 % to 19 %. This corresponds to a relative risk reduction of 58 % (confidence interval [95 % CI] 35–78) and only four patients as the number needed to treat. This is largely due to a relative risk reduction of 69 % (38–84) for wound complications. Intensive and brief behavioral interventions both induced smoking cessation. It is important, however, to notice that only intensive preoperative behavioral interventions reduced surgical complications and achieved sustained behavioral change.
The preoperative physical status of the individual patient has an obvious impact on his or her tolerance of major surgery, multimodal treatment, and their consequences. Assessment and correction of reduced general condition require additional resources and have been neglected so far. This is true in particular for preoperative physiotherapy (called prehabilitation).
A recent publication suggested a simple walking test (the Timed Up and Go test) as a reliable detection tool that is easy to perform and has a high predictive value for postoperative morbidity and mortality . The next logical step is to strive to improve a patient’s reduced physical condition. Initial works in different fields of surgery have been promising, especially with regard to reducing cardiopulmonary morbidity [25, 35]. There is no established standard, however, and adopted protocols differ widely. Furthermore, reported outcome measures were poorly standardized and heterogeneous .
The McGill group from Montréal recently reported that pre- and postoperative physical ability of patients undergoing colorectal surgery could be improved by two different exercise programs. However, the adherence to physical exercise programs was low, and a clear link between enhanced physical status and improved clinical outcomes has not yet been established . Nonetheless, the rationale behind and the available data should encourage the pursuit of this approach.
36.3.2 Nutritional Screening and Perioperative Nutrition
Malnutrition is probably the most prevalent modifiable risk factor for adverse outcomes and infectious complications in particular. This condition affects up to 40 % of patients undergoing major surgery. It has been convincingly shown that malnourished patients have at least twice the risk of developing overall and major complications sorensen clin nutr 2008 (EuroOOPS).
The European and American guidelines (ESPEN, ASPEN) therefore recommend routine nutritional screening for every patient before undergoing major surgery. Several screening tools have been proposed and validated in large prospective cohorts: the nutritional risk score (2002), The Malnutrition Universal Screening Tool, and the subjective global assessment. Preoperative weight loss remains one of the most reliable criteria to guide nutritional interventions; serum albumin and prealbumin can also be used as screening parameters and to monitor the efficacy of nutritional support [9, 51].
Pre- or perioperative nutrition is recommended for all patients who are (1) scheduled for major surgery and (2) malnourished or at nutritional risk according to the screening tool used. Most patients can be conditioned with oral nutritional supplements for 5–7 days before surgery, whereas severely malnourished patients might require enteral or even parenteral nutrition for at least 2 weeks; in these patients, surgery needs to be postponed.
Immunonutrition has been suggested as a specific nutritional formula not only to improve nutritional status but also primarily to modulate the immune response. The active ingredients arginine, glutamine, n-3-fatty acids, and ribonucleic acid help to enhance cellular and humoral immune function and to modulate an excessive immune response in the postoperative phase. Several systematic reviews have evaluated its clinical effects. In 21 RCTs (2,730 patients), overall and infectious complications were halved in patients receiving perioperative immunonutrition. This translated into reduced hospital stays (>2 days) and costs. Mortality was not different between the groups. Consistent outcomes were found for the subset of colorectal patients and when including only high-quality studies. Nevertheless, a significant heterogeneity between the studies does not permit immunonutrition to be uncritically recommended to all patients [10, 51].
36.3.3 Bowel Preparation: Sense or Nonsense?
Mechanical bowel preparation is another long-standing dogma in colorectal surgery that has been challenged only recently. The obvious rationale was to avoid intestinal spillage and intraoperative contamination, and hence to reduce surgical site infection rates. Furthermore, an empty colon tends to be easier to handle. The downsides of mechanical bowel preparation seem obvious as well: major fluid shifts, electrolyte losses, and bowel wall alterations with impaired barrier function. Furthermore, the risk of intestinal spillage seems to be increased even in prepped patients with liquid colonic content.
A Cochrane collaboration summarized the available evidence on preoperative bowel preparation on postoperative outcomes in four systematic reviews since 2003. The latest update is based on 18 RCTs including 5,805 subjects . No statistical difference was observed for anastomotic leak rate or wound infections after colon and rectal resections, respectively. The authors and subsequent guidelines suggested that bowel preparation should be omitted before colon surgery but may be selectively used for low rectal resections [17, 20, 33].
This cautious specification for rectal surgery is the result of GRECCAR III, a French multicenter study. Bretagnol and colleagues  reported significantly more overall and infectious complications as well as a trend toward a higher leak rate in patients undergoing rectal resections without mechanical bowel preparation. However, these results have not yet been confirmed by other randomized studies and contrast with the results of the Cochrane review. It is worth mentioning, however, that bowel preparation is still widely practiced despite the convincing evidence against its use.
In summary, bowel preparation should not be used for right or transverse colectomies, whereas retrograde enemas are accepted before left-sided resections. A full anterograde bowel preparation should be reserved for specific situations such as intraoperative colonoscopy to locate a tumor and the creation of a neovagina, and should be further studied in the case of low anterior resections of the rectum.
36.3.4 Steroids: From Foe to Friend?
Steroids have been demonized for decades and are still feared by many surgeons for their negative impact on immune defense and wound healing. Indeed, chronic steroid use seems to increase infectious complications, especially after rectal resections. The effect on wound healing seems to be time- and dose-dependent. Even high-dose corticosteroids have not been associated with adverse outcomes if administered for <10 days before surgery. Other studies reported more wound complications only for patients on high-dose corticosteroids for at least 30 days. The threshold dosage in most studies is around 20 mg/day of prednisone [34, 39].
Single-dose preoperative administration of corticosteroids was suggested many years ago to dampen an excessive postsurgical stress response and thus to positivley influence surgical outcomes. While wound problems remained unaffected, a decrease in pulmonary complications was observed. Dexamethasone has been studied extensively with regard to its effect on postoperative nausea and vomiting, and the literature was recently summarized by a systematic review of 60 RCTs including 6,696 participants. By a single dose of 4–5 mg dexamthasone, incidence of postoperative nausea and vomiting was largely reduced, achieving an odds ratio of 0.31 (95 % CI 0.23–0.41) and a number needed to treat of only 3.7 (95 % CI 3.0–4.7). No further clinical benefit was observed when comparing 4–5 mg of dexamethasone with higher doses (8–10 mg) .
Low-dose steroids are successfully used as an adjunct pain treatment in multimodal pathways. According to a systematic review of 45 RCTs (5,796 patients), patients receiving dexamthasone at a dose between 1.25 and 20 mg benefitted from a lower postoperative pain score, reduced opioid consumption, less rescue analgesia, and a shorter stay in the recovery room when compared with the control group. No negative effect on wound healing was noted, and blood glucose levels increased only moderately. The clinical benefits were not related to the dose of dexamethasone . Therefore, most modern perioperative care pathways suggest preoperative administration of dexamthasone at a dose of 4–8 mg.
36.3.5 Avoidance of Surgical Site Infections
Wound infections are a deplorable but, at the same time, an inevitable risk after colorectal surgery. Honest reporting and clinical follow-up situate surgical site infection (SSI) rates after colorectal surgery around 20 % after open resections and around 10 % after laparoscopic resections. Much “lower” SSI rates are reported from US centers, where a chart-based review is performed for surveillance of SSIs. This is an important methodological difference when comparing SSI between centers, especially as a quality parameter. The better a patient’s follow-up, the higher are the SSI rates!
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