Assessing organ function in the critically ill patient

INTRODUCTION Organ dysfunction and failure are common causes of morbidity and mortality in critically ill patients and assessment of the degree and evolution of dysfunction can help with severity assessment. This is particularly important in clinical trials to appreciate the severity of illness and compare groups of patients. The sequential organ failure assessment (SOFA) score was developed to “describe quantitatively and as objectively as possible the degree of organ dysfunction/failure over time” some 30 years ago by a group of intensivists gathered together by the European Society of Intensive Care Medicine (ESICM).[1] The meeting was held in Versailles (France) over a couple of days, and the proposed score was then validated on existing databases.[2] Of particular note, the SOFA score was not designed to predict outcome (unlike, e.g., the Acute Physiology and Chronic Health Evaluation [APACHE] score), even though the degree of dysfunction is correlated with outcome,[2,3] but to simply describe the degree of organ dysfunction, using a scale. During the development process, the working group decided to apply a number of principles to the scoring system:[1] 1. Organ dysfunction is a continuum (not an all-or-none phenomenon), so the variables used to assess it should also have ranges and not be simply present or absent (e.g., diagnoses could not be included as variables); 2. Organ dysfunction changes over time (a dynamic process), and should therefore be assessed at regular intervals. Variables thus need to be easily measurable at regular intervals-preferably daily- so that the time course can be evaluated and followed; 3. Organ dysfunction can vary in severity across organs and over time from one organ to another, so it should be possible to separate the function of different organs in addition to having a single composite score; 4. The metrics used to assess organ function should meet several criteria (Table 1). Most importantly, the score should be simple, easy to use, with a limited number of variables that are accessible in every institution around the globe. After some discussion, the group decided to limit the evaluation to the function of six organs: respiratory, cardiovascular, neurological, renal, haematological, and hepatic. Table 1. - Principal characteristics of the metrics used Number Characteristic 1 Should be continuous (no diagnoses) 2 Should be objective (data collection should be automated whenever possible) 3 Simple, easily available but reliable 4 Obtained routinely and regularly in every institution 5 Specific for the function of the organ considered 6 Independent of the type of patient (and therapy wherever possible) Interestingly, the SOFA score was initially developed for application in sepsis, so was called the “Sepsis-related” Organ Dysfunction Assessment Score. The word “Sepsis-related” was quickly changed to “Sequential”, following the suggestion of a reviewer after initial submission to a scientific journal for publication, as the score is equally applicable to all patients with critical illness. Intensive care medicine has evolved over the last three decades, with new treatments available to support the different organs and some no longer available or used; the need to update the SOFA score has therefore been raised.[4] Here we will consider possible options on an organ by organ basis, discussing first the situation at the time of original score development and thus currently, and then potential changes that could be included in a new version of the score. RESPIRATORY SYSTEM Current score As the score primarily evaluates hypoxic (not hypercapnic) respiratory dysfunction, the primary variable selected was the PaO2/FIO2 ratio. It was considered that a respiratory failure score of 3 or 4 should be accorded only when some form of respiratory support, including non-invasive mechanical ventilation, is being given. Indeed, in some patients, gas exchange can improve substantially as soon as some positive pressure is applied, as a consequence of opening previously collapsed or poorly ventilated alveoli. The degree of continuous positive airway pressure or positive end-expiratory pressure applied was not included in the score, to keep it simple. Implicitly, use of venovenous extracorporeal membrane oxygenation (VV-ECMO) reflects severe respiratory failure, and should lead to a score of 4. How the score could be updated With the move toward less invasive monitoring, blood gas analysis is less often required or performed, especially in some US centers, and oxygen saturation measured by pulse oximetry (SpO2) could be introduced,[5] although it is a less precise evaluation. High flow oxygen administration is increasingly used and could be introduced into the score as a form of “respiratory support”, with little consequence on the score value. Use of VV-ECMO could be explicitly mentioned as leading to a score of 4. CARDIOVASCULAR SYSTEM Current score Although it was acknowledged that this was not ideal because of possible variation in practice and drug availability across units,[1] cardiovascular dysfunction is assessed principally by therapeutic requirements, in particular the use of vasoactive agents. Cardiovascular failure associated with a SOFA score of 3 or 4 reflects shock and therefore requires the administration of vasopressors. A score of 2 reflects dysfunction without shock and is best expressed by administration of dobutamine, the primary inotropic agent used in the intensive care unit (ICU). Lower degrees of dysfunction rely on mean arterial pressure measurements although the broad cut-offs chosen may not apply to all individuals. As for the use of VV-ECMO in respiratory failure, the use of veno-arterial (VA) ECMO should lead to a score of 4. The inclusion of blood lactate levels was discussed during the initial score development but was discarded as changes in lactate levels can be relatively slow, so that a patient may be already resuscitated but still have some degree of remaining hyperlactataemia. How the score could be updated Dopamine use has been abandoned and can be eliminated from the score. Vasopressin (and derivatives) could be added as part of scores 3 or 4, although this will not change the score value much. One could also consider the use of angiotensin II within a score of 4: although it is not widely used today, there is a sound rationale for administration in some cases so that it may be used more widely in the near future.[6] Other vasopressor substances, such as phenylephrine, methylene blue, and hydroxocobalamin, are seldom used, and their addition would make the score more complicated, with uncertain benefit. One could explicitly add the use of VA-ECMO within a score of 4, and also the use of mechanical circulatory support devices, such as the Impella system (Abiomed, Danvers, MA, USA). Importantly, use of VA-ECMO to give a score of 4 for the cardiovascular system should not be combined with VV-ECMO in the respiratory subsection. NEUROLOGICAL SYSTEM Current score Neurological dysfunction is assessed using the Glasgow coma scale (GCS) score. A major issue with this system is the still frequent use of sedation, which can induce a pharmacological alteration of consciousness and thus influence the GCS evaluation. The “assumed” GCS should therefore be taken into consideration, i.e., the score that the patient would have in the absence of sedation.[3] For example, a patient anaesthetized for a surgical procedure should not be considered as a patient with neurological failure if full neurological recovery is expected after surgery; a normal GCS should be “assumed” accordingly. How the score could be updated It is difficult to find an alternative primary metric of neurological function that could be used within a simple scoring system such as SOFA. Formal, standardized recording of the “assumed” GCS in the patient data management system may help, to enable automated collection of data. Electroencephalography can be suggested but is not routinely used in the majority of patients, requires training for interpretation, and is not available in some centers. RENAL SYSTEM Current score Renal function is assessed using both blood creatinine concentrations and urine output. The two variables should be considered together in all patients. For example, a patient can become oliguric when they develop shock while serum creatinine has not yet had time to increase. Conversely, there may be some alteration in creatinine concentration although urine output is maintained. Renal replacement therapy (RRT) indicates presence of complete renal failure, which results in a score of 4. It is generally associated with oliguria, so that this is not important. How the score could be updated RRT could be mentioned explicitly in the SOFA table, although the need for simplicity should prevail. HAEMATOLOGICAL SYSTEM Current score Haematological function is evaluated using the platelet count, a reliable measure as it can be low even in the absence of overt coagulopathy. It may even be one of the only signs of sepsis. The platelet count is not influenced much by platelet transfusion, because most patients receiving platelet transfusions still have some degree of thrombocytopaenia. How the score could be updated Presence of coagulopathy is an important indicator of haematological dysfunction, but is difficult to measure accurately, and can be secondary to liver dysfunction. The presence of anaemia could be included in this subscore, but the leucocyte count is not very informative. HEPATIC SYSTEM Current score It is difficult to find a sufficiently sensitive marker of liver dysfunction and the working group eventually selected the blood bilirubin level as the best available option, considering that haemolysis is relatively rare in the critically ill patient. Nevertheless, this variable is limited because concentrations increase and decrease relatively slowly during critical illness. How the score could be updated The prothrombin time (PT) alone is not suitable as it is primarily a coagulation marker. Liver enzymes could be added to the score and were considered in the initial development. However, liver transaminases can be released by other organs, including the muscle in particular. OTHER POSSIBLE ORGAN SYSTEMS THAT COULD BE INCLUDED Several other organ systems could be included in an updated SOFA score, including metabolic, gastrointestinal and immunological systems. The metabolic system was considered by the original working group, but assessment would primarily have included the need for insulin, which is largely determined by the past history of the patient, and also influenced by local glucose control policies, so it was discarded. Likewise the assessment of gastrointestinal function was considered too difficult and unreliable to be included. Abdominal hypertension is important but concerns just a small proportion of ICU patients. Immunological alterations are difficult to assess and to interpret. The easiest way would be to include an increase in C-reactive protein (CRP), but this measure may not truly reflect any specific form of organ dysfunction; more sophisticated tests cannot be measured everywhere. Moreover, immunological alterations are hard to interpret, as the immune function may be abnormally stimulated in severe acute inflammatory responses but also be depressed (acquired immunosuppression) later in such crises. MODIFIED SOFA SCORES Several modified SOFA scores have been proposed, including some that require fewer laboratory measurements,[7] remove some organ subscores,[8] replace individual variables, for example, using peripheral oxygen saturations instead of the PaO2/FIO2 ratio,[7] or add additional factors.[9] However, none has been convincing or widely used, except perhaps for special populations, such as patients with chronic liver failure, in which the international normalized ratio (INR) and a measure of hepatic encephalopathy are included.[10] CONCLUSION An updated or completely new version of the SOFA score incorporating some of the elements discussed and bringing it inline with current clinical practice would be welcome.[4] However, regardless of which new components are included, a new score will not fundamentally alter the way in which we currently assess organ dysfunction over time. Importantly, in whichever way a new version of the score is developed, it should remain true to the principles set out in the original process and be easy to use and accessible to all centers.