aphorism that dates back to the early days of medicine, but is still widely used to .... Patients with severe sepsis are often treated in an intensive care unit (ICU) ...
93
Source Control in the ICU J.J. De Waele, M.M.L.G Malbrain, and I.E. De Laet
III Introduction Source control is generally considered one of the oldest, most important and most obvious strategies in the management of infections. ‘Ubi pus ibi evacua’ is a Latin aphorism that dates back to the early days of medicine, but is still widely used to stress the importance of source control. Although source control is generally considered to be the cornerstone of the management of several infections, it is also the least ‘hyped’ strategy, and therefore gets little overall attention in the literature. In the Surviving Sepsis Campaign guidelines [1], the focus is mostly on resuscitation, antibiotic treatment, and ancillary strategies such as anti-inflammatory therapies, and source control may, therefore, appear underappreciated. A lot of questions remain unanswered regarding the necessity, timing, and methodology of source control, and how these factors impact the outcome of patients with sepsis. A possible explanation for the relative lack of apparent interest in source control may lie in the perception that the source control of infection is only a problem in surgical infections, and once, this was indeed true. The ‘source control’ concept originated in the management of complicated intra-abdominal infections, but over time, physicians treating various types of infection realized that this concept and the components it consists of, can be applied to other surgical and non surgical infections.
What is ‘Source Control’? In the context of complicated intra-abdominal infections, source control is often defined as the purely mechanical control of gastrointestinal content leaking into the peritoneal cavity. Surgeons often intuitively feel that source control equals surgery, rather than considering the surgical intervention to be part of a source control approach to the patient with intra-abdominal infections. The concept ‘source control’ consists of ‘all physical measures undertaken to eliminate a source of infection, to control ongoing contamination, and to restore premorbid anatomy and function’ [2]. All the different aspects of this definition are important, but the elimination of the source and the control of ongoing contamination determine the early and long term success of the treatment. Restoration of anatomy and complete function can be performed in a delayed fashion when prolonging the surgical intervention may be harmful to the patient at the first operation (which is the basis of the ‘damage control’ concept). Although this definition may seem straightforward, it describes the desired result instead of the proposed technique used to get there. Therefore, it is no surprise that
94
III
J.J. De Waele, M.M.L.G Malbrain, and I.E. De Laet
source control can be interpreted in different ways, and that ‘adequate source control’ is not clearly defined. There are few data on the interobserver agreement of what adequate source control means when applied to a particular patient. In a recent study, Suding et al. studied 247 patients who failed treatment for complicated intraabdominal infection. Interobserver agreement between two independent experts was (very) low, especially in patients with abscesses and in more severely ill patients [3]. It is not clear what impact this has on the management of the critically ill patient.
Elements of Source Control Source control is based on four principles: Drainage, debridement, decompression and restoration of anatomy and function. All four principles are important as such, but in the individual patient, they can be applied independently, and at different moments; this is especially relevant in the critically ill patient, and obviates the need for involvement of intensivists regarding the timing and extent of the procedure in the critically ill patient.
Drainage Drainage consists of evacuating the contents of an abscess, and by so-doing, creating a controlled fistula – if there is a connection to an epithelium lined lumen, such as an intestine – or creating a sinus if there is no such connection. The efficiency of the drain used is very important: It should be sized adequately to allow complete evacuation of the abscess. If the abscess cannot be drained completely, source control will fail. The use of additional drains can be considered, but it should be remembered that some abscesses or infections cannot be drained adequately. In these instances, debridement of necrotic tissues or removal of gastrointestinal contents may be necessary. Drainage of an abscess can be performed surgically or percutaneously, often using ultrasound or computed tomography (CT) scan [4]. Percutaneous drainage is preferred for most situations, provided that adequate drainage is possible, and no debridement or repair of anatomical structures is necessary. Percutaneous drainage can also be used as a temporizing strategy even if debridement is indicated, or resection of part of the gastrointestinal tract is necessary. Especially in critically ill patients, where a surgical intervention can be difficult because of inflammation at the site of the infection and coagulopathy, this approach may be a valuable alternative. Surgical drainage is indicated when percutaneous drainage fails, or when percutaneous drainage cannot be performed, for example when multiple abscesses are present, or when the presence of bowel loops between the abdominal wall and the abscess prevent passing a needle and guidewire to introduce the drain. It is often difficult to recognize failure of percutaneous drainage, but the clinical picture of ongoing sepsis a few days after percutaneous drainage should trigger a new search for a residual infection. In most cases, failure of percutaneous drainage is caused by ongoing contamination of the abscess due to a connection with an intestine, ineffective drains (too small for the content to be drained), or presence of tissues that need debridement. At this point, the aspect or volume of the drain effluent is notoriously unreliable and should not be used as a basis to guide therapy.
Source Control in the ICU
95
Decompression Decompression may involve decompressing distended bowel in cases of (impending) obstruction or of intra-abdominal hypertension (IAH).
Debridement Debridement should consist of removing dead tissue and foreign material from the abdominal cavity. This can only be accomplished surgically, and the extent to which this should be done remains a controversial topic. Some surgeons favor a minimalistic approach, which consists of removing dead tissue and using gauze to remove any pus present, whereas others promote an aggressive approach of high volume peritoneal lavage, and meticulous removal of all fibrin adherent to the intestines or abdominal wall. The latter carries a higher risk for iatrogenic bowel injuries, and has also been associated with a higher rate of postoperative abscesses. Therefore, a minimal aggressive approach should be preferred.
Restoration of Anatomy and Function Restoration of anatomy and function is the final step in the management of complicated intra-abdominal infections, and as such often the goal of the surgical intervention. Examples are the perforation of the gastric ulcer that needs closure, or the inflamed appendix that needs resection. In most patients, restoration of anatomy and function can be established at the first operation, but in some patients, it needs to be delayed until the condition of the patient allows a sometimes lengthy procedure, and until tissue healing is adequate. This should be assessed on an individual basis but, generally, it is advised not to unnecessarily prolong surgical intervention in patients who are in shock, or who have severe organ dysfunction. In patients with severe acute pancreatitis who were treated surgically, we found that severity of disease at the moment of surgery was independently associated with increased mortality [5]. In some patients, this delay of a definitive procedure can take months, and the patient may even be discharged home before an attempt is made to restore anatomy and function, for example, restore continuity in a patient who underwent Hartmann’s procedure for perforated diverticulitis.
Do we need to perform Source Control? Although the application of source control in the treatment of infections seems only logical, a firm scientific basis for this is lacking. No controlled randomized trial has been performed, and the limited data available come from descriptive studies in which an increased mortality is reported in patients with intra-abdominal infections who were managed non-operatively [6, 7]. Koperna and Schulz described increased mortality when surgery was delayed for more than 48 hours in patients requiring relaparotomy for persistent abdominal sepsis; this effect was observed in all patients irrespective of the severity of disease, and was almost 100 % in patients with APACHE II scores of 20 or higher who were not operated on in time [8]. In another study in patients with complicated intra-abdominal infections, failure to clear the abdomen resulted in a much higher risk for dying, but also timing proved to be
III
96
III
J.J. De Waele, M.M.L.G Malbrain, and I.E. De Laet
important, with increasing mortality when source control was delayed [9]. This has also been demonstrated in patients with necrotizing skin and soft tissue infections [10], but for most types of infection, data are lacking. In infected pancreatic necrosis, it has been suggested that source control can or should be delayed until after the first 2 to 3 weeks [11, 12]. An increased mortality has been described in patients undergoing early surgery [13], but it should be considered that the majority of these patients did not have infected, but sterile, pancreatic necrosis. It is not clear if the increased mortality rate in a prospective study [14] of early versus late surgery was not caused by the surgical procedure and complications related to that surgical procedure. Other studies could not find a survival benefit of delaying surgery [15]. The decision to intervene in patients with infected pancreatic necrosis should be based on the clinical condition of the patient, the location and extent of the necrosis, but above all, should be individualized.
When to Perform Source Control? Source control can and should be applied in the management of all patients presenting with sepsis, and not only in patients with surgical infections such as intraabdominal infections or necrotizing skin and soft tissue infections, two conditions most often associated with source control. Although it may appear more important in the two above examples, removal of infected devices, drainage of abscesses and removal of necrosis is important in any kind of infection, irrespective of the focus.
The Role of the Intensivist Patients with severe sepsis are often treated in an intensive care unit (ICU) from the moment the diagnosis is established, and the intensivist is routinely involved in the management of these patients. In parallel, the role of surgical and medical specialities on the ICU is decreasing, especially in closed units. The role of the intensivist is crucial to determine the need for, timing and extent of source control measures that should be applied to the patient. Establishing a diagnosis is an essential first step in this process. This not only requires obtaining appropriate cultures, but also the identification of the focus of the infection. Thorough clinical examination, imaging techniques when necessary, and directed diagnostic studies should be performed in parallel with fluid resuscitation, empiric antibiotic administration, and supportive measures. Once a diagnosis has been obtained, the concept of source control should be applied to the patient and the search for a focus of infection that is amenable to one or more elements of the source control approach should be undertaken. Table 1 lists a number of common infections with specific issues that should be considered in each case. When a patient has already undergone a source control procedure, it is even more challenging to recognize failed source control, and determine the need for a new intervention. The next step is to determine the optimal intervention for the needs of the patient. It is obvious that adequate source control should aim at eliminating infection and controlling ongoing contamination. But adequate source control goes beyond that, acting to cause minimal damage to the patient and his/her physiology; this narrow balance between fully eradicating the infectious focus from the patient
Source Control in the ICU
97
Table 1. Source control measures for specific infections Clinical (suspected) diagnosis
Consider
Source control
Pneumonia
Empyema
Drainage of pleural effusion
Secondary peritonitis
Ongoing contamination due to perforation
Exteriorization of leaking GI tract, drainage of peritoneal fluids
Pancreatitis
Infected pancreatic necrosis
Debridement of necrotic tissue
Urinary tract infection
Catheter-related urinary tract infection
Remove catheter
Bacteremia
Catheter-related blood stream infection
Remove catheter
Skin and soft tissue infections
Necrotizing skin and soft tissue infections
Resection of necrotic tissue – explore when suspected on clinical grounds
Pyelonephritis
Urinary tract lithiasis
Debridement – lithiasis removal
Mediastinitis
Esophageal perforation
Surgical drainage
Sinusitis
Abscess formation
Aspiration and drainage – remove nasogastric/nasotracheal tube
Acalculous cholecystitis
Abscess, hydrops
Percutaneous drainage – cholecystectomy
Pericarditis
Drainage of pericardial fluid
Table 2. Indications for surgical versus percutaneous drainage Percutaneous drainage preferable One well defined abscess Absence of ongoing contamination from gastrointestinal tract or other focus Thin contents No or minimal associated necrosis ‘Hostile’ abdomen Difficult to access visceral abscess
Surgical drainage preferable Multiple abscesses Ongoing contamination from gastrointestinal tract or other focus Associated necrosis Thick contents Failed percutaneous drainage Infected pancreatic necrosis Abscess inaccessible to percutaneous drainage (e.g., interloop abscess)
and limiting harm to the patient, is crucial in the management of infections, especially in the critically ill, in whom additional intraoperative damage may have dramatic consequences. Drainage, as an example, can be accomplished by surgery or by percutaneous drainage. Table 2 lists the conditions that may favor a surgical or percutaneous approach. When debridement is necessary in addition to drainage, a surgical approach may be preferred. The timing of surgery is also essential, yet often difficult to determine in individual cases.
III
98
J.J. De Waele, M.M.L.G Malbrain, and I.E. De Laet
What if Source Control is Impossible or Fails?
III
In some patients, source control is impossible to accomplish in one surgical intervention, because the disease process cannot be completely eradicated during the surgical procedure, e.g., in patients with retroperitoneal necrosis, diffuse peritonitis or intestinal ischemia. Although source control may fail in all infections, this is a typical problem in critically ill patients with complicated intra-abdominal infections. Those patients are candidates for more aggressive strategies like open abdomen treatment, or planned re-laparotomies. On-demand re-laparotomies are associated with reduced costs and use of hospital resources in this setting [16]; use of planned re-laparotomy as a routine strategy in the management of patients is no longer warranted. However, both options should be part of the armamentarium of the surgeon dealing with severe complicated intra-abdominal infections, rather than sticking unconditionally to either. Several techniques are available to temporarily close the abdomen without creating insurmountable nursing problems. Failed source control often has a dramatic impact on postoperative morbidity and mortality, and is more important in determining outcome than antibiotic failure. Usually, it is the consequence of inadequate surgery – bad choice of type of operation, bad timing or bad technique – although patient factors with a ‘hostile’ abdomen and fragile intestines are also important. Severe sepsis and multiple organ dysfunction syndrome are systemic consequences of persistent infection, but local complications may also occur, such as IAH. Diagnosis of failed source control is often difficult, and clinical examination is often unreliable. Imaging can be helpful, but in some patients explorative laparoscopy or -tomy must be used as a diagnostic tool as well [17], especially in patients in whom intestinal ischemia is suspected. The therapy of complicated intra-abdominal infections can itself cause numerous complications, which further compromise the outcome. Intraoperative trauma to intestines is common, but erosion of drains into blood vessels or intestines is also possible. Surgical intervention can add to the trauma, and perforation during insertion of percutaneously placed drains can also occur. In these patients, open abdomen techniques are often used to deal with the ongoing peritonitis, and planned or unplanned re-laparotomies may be necessary to deal with recurrent intraabdominal abscesses and collections. This clinical picture of persistent or recurrent peritonitis, nowadays referred to as tertiary peritonitis, has been associated with a high mortality rate [18]. Often infection with nosocomial organisms such as methicillin-resistant Staphylococcus aureus (MRSA), methicillin resistant coagulase-negative staphylococci, Pseudomonas or Candida species is found, although it is difficult to discriminate between infection and colonization. It is not clear if tertiary peritonitis is a cause rather than a consequence of disease severity [19], and a clear definition of the syndrome is lacking.
Special Considerations in Critically Ill Patients Timing of Source Control As a general rule, the source control procedure should be performed as soon as possible, and certainly within 6 hours after diagnosis. Stabilization of the patient is highly desirable before any source control procedures are started, but stabilization may not be feasible in some patients. Planning of the procedure and discussion with
Source Control in the ICU
99
the surgeon and/or other specialities involved should take place before stabilization is accomplished.
Definitive Therapy or Temporary Measures As addressed before, collateral damage inflicted by the source control procedure should be minimal, and therefore, a minimally invasive procedure performed at the bedside is to be preferred, provided that it fulfils the requirements of an adequate source control procedure. Obviously, the risks of general anesthesia, or transportation to the interventional radiology suite should be weighed against the benefit of a more directed or definitive procedure. In patients with borderline coagulation parameters, surgical blood loss may add to the risk for postoperative bleeding and complications related to it. The ongoing need for resuscitation should not be used as an argument against a source control procedure; fluid resuscitation should continue when a patient leaves the ICU, and full monitoring should be available at any location where this kind of patient is treated. Damage control principles should be applied when physiology is unstable (impaired coagulation, metabolic disturbances with acidosis, hypothermia, and poor tissue perfusion among many). The patient should be returned to the ICU as soon as possible for correction of these disturbances; completion of the surgical procedure, including restoring gastrointestinal continuity or proper wound closure, can be deferred until circumstances are more favorable. In case of rapidly progressive disease, with necrotizing fasciitis as a typical example, the same principles apply, but stabilization should not be pursued before surgery is performed. Bedside procedures are often recommended in these cases to gain time and to avoid transportation to the operating room.
How to Recognize Failed Source Control? This is one of the most challenging issues, depending on the location of the infection. When there is ongoing necrosis in patients with necrotizing skin and soft tissue infections, or overt leakage of gastrointestinal contents from an open abdominal wound, the diagnosis of failed source control is obvious, and the need for re-intervention easily established. When there is failed source control in closed spaces such as the peritoneum or pleura, it is far more difficult to confirm the clinical suspicion. Currently, there is no diagnostic test available for failed source control; the use of simple inflammatory mediators such as fever, white blood cell count or C-reactive protein (CRP), may be limited by the occurrence of infections at other sites in ICU patients. Recently, Lepouse et al. retrospectively studied the role of procalcitonin as a predictor of the need for re-laparotomy; the authors found that persistent elevation of procalcitonin levels was associated with positive findings at re-laparotomy [20]. An important predictor seems to be the dynamics of organ dysfunction. When the patient further deteriorates, or deteriorates after initial improvement, this may be an indication that there is ongoing uncontrolled infection. This can be assessed by calculating daily sequential organ failure assessment (SOFA) scores. Recently, van Ruler et al. looked for parameters associated with positive findings at re-laparotomy after previous surgery for secondary peritonitis [21]. Age (OR 0.97, per 10 year), postoperative fever > 39 °C (OR 6.24), PaO2/FiO2 ratio (OR 0.99), heart rate (OR
III
100
III
J.J. De Waele, M.M.L.G Malbrain, and I.E. De Laet
1.02) and the postoperative hemoglobin level (OR 0.41) were all significantly associated with the need for re-laparotomy. Remarkably, none of the intraoperative findings, such as extent of peritonitis, etiology or focus of the intra-abdominal infection, played a role when the postoperative variables were entered in the model. Systemic bacteremia may also give a clue. In a study on blood stream infections of abdominal origin, the occurrence of a breakthrough blood stream infection (defined as an infection occurring after at least 48 hours of adequate antibiotic therapy) pointed to inadequate source control in 13/18 patients [22]. When failed source control is suspected based on any of the above parameters, the next step is to confirm this when there is no clear-cut indication for re-laparotomy; in some patients, obvious abdominal findings such as rebound tenderness or guarding with or without other signs or symptoms may be enough to advocate reexploration. For obvious reasons, the role of clinical examination of the abdomen may be limited in the ICU; when findings are negative, few conclusions can be drawn from it, but when positive, they remain a very important tool. Consultation with the surgeon who performed the original surgical procedure is mandatory, as specific details of the surgical procedure may be helpful to guide further management of the patient. In some patients with a high probability of failed source control, for example a patient with gastrointestinal ischemia where borderline ischemic bowel was left in situ, a planned re-laparotomy should be considered. As a general tool, the use of planned re-laparotomy has not been demonstrated to be superior in the management of complicated intra-abdominal infections.
Conclusion Source control is the cornerstone of the management of surgical infections, and antibiotics should be considered not more than an adjunct to source control. But source control also has an important role in non-surgical infections, and the need for source control should be evaluated early in the management of patients with severe sepsis. The critically ill patient is a unique challenge, as the physiology of the patient may make diagnosis more difficult and such patients may require specific interventions as a temporizing strategy. The role of the intensivist is essential in determining the specific needs of the patient, and in tailoring the therapeutic strategy to the individual patient. Adequate source control goes beyond source control per se, and includes optimal type and timing of the intervention and limited damage to the anatomy and physiology of the patient.
References 1. Dellinger RP, Levy MM, Carlet JM, et al (2008) Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med 34: 17 – 60 2. Schein M, Marshall J (2002) Source Control. A Guide to the Management of Surgical Infections. Springer, Heidelberg 3. Suding PN, Orrico RP, Johnson SB, Wilson SE (2008) Concordance of interrater assessments of surgical methods to achieve source control of intra-abdominal infections. Am J Surg 196: 70 – 73 4. Montgomery RS, Wilson SE (1996) Intraabdominal abscesses: image-guided diagnosis and therapy. Clin Infect Dis 23: 28 – 36 5. De Waele J, Hoste E, Blot S, et al (2004) Perioperative factors determine outcome after surgery for severe acute pancreatitis. Crit Care 8: R504 – R511
Source Control in the ICU 6. Wacha H, Hau T, Dittmer R, Ohmann C (1999) Risk factors associated with intraabdominal infections: a prospective multicenter study. Peritonitis Study Group. Langenbecks Arch Surg 384: 24 – 32 7. Grunau G, Heemken R, Hau T (1996) Predictors of outcome in patients with postoperative intra-abdominal infection. Eur J Surg 162: 619 – 625 8. Koperna T, Schulz F (2000) Relaparotomy in peritonitis: prognosis and treatment of patients with persisting intraabdominal infection. World J Surg 24: 32 – 37 9. Mulier S, Penninckx F, Verwaest C, et al (2003) Factors affecting mortality in generalized postoperative peritonitis: multivariate analysis in 96 patients. World J Surg 27: 379 – 384 10. Elliott DC, Kufera JA, Myers RA (1996) Necrotizing soft tissue infections. Risk factors for mortality and strategies for management. Ann Surg 224: 672 – 683 11. Muller CA, Vogeser M, Belyaev O, et al (2006) Role of endogenous glucocorticoid metabolism in human acute pancreatitis. Crit Care Med 34: 1060 – 1066 12. Nathens AB, Curtis JR, Beale RJ, et al (2004) Management of the critically ill patient with severe acute pancreatitis. Crit Care Med 32: 2524 – 2536 13. De Waele J, Vogelaers D, Decruyenaere J, et al (2004) Infectious complications of acute pancreatitis. Acta Clin Belg 59: 90 – 96 14. Mier J, Leon EL, Castillo A, et al (1997) Early versus late necrosectomy in severe necrotizing pancreatitis. Am J Surg 173: 71 – 75 15. De Waele JJ, Hoste E, Blot SI, et al (2004) Perioperative factors determine outcome after surgery for severe acute pancreatitis. Crit Care 8: R504 – 511 16. van Ruler O, Mahler CW, Boer KR, et al (2007) Comparison of on-demand vs planned relaparotomy strategy in patients with severe peritonitis: a randomized trial. JAMA 298: 865 – 872 17. Hutchins RR, Gunning MP, Lucas DN, et al (2004) Relaparotomy for suspected intraperitoneal sepsis after abdominal surgery. World J Surg 28: 137 – 141 18. Nathens AB, Rotstein OD, Marshall JC (1998) Tertiary peritonitis: clinical features of a complex nosocomial infection. World J Surg 22: 158 – 163 19. Evans HL, Raymond DP, Pelletier SJ, et al (2001) Tertiary peritonitis (recurrent diffuse or localized disease) is not an independent predictor of mortality in surgical patients with intraabdominal infection. Surg Infect (Larchmt) 2: 255 – 263 20. Lepouse C, Murat O, Nicolai F, et al (2008) Postoperative procalcitonin kinetics: An indicator for therapeutic strategy in peritonitis? Intensive Care Med 34 (Suppl 1):S123 (abst) 21. van Ruler O, Lamme B, Gouma DJ, et al (2007) Variables associated with positive findings at relaparotomy in patients with secondary peritonitis. Crit Care Med 35: 468 – 476 22. De Waele JJ, Hoste EA, Blot SI (2008) Blood stream infections of abdominal origin in the intensive care unit: characteristics and determinants of death. Surg Infect (Larchmt) 9: 171 – 177
101
III
