University of Groningen Rational clinical examination of the critically ill patient Hiemstra, Bart

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University of Groningen

Rational clinical examination of the critically ill patient

Hiemstra, Bart

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Publication date: 2019

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Hiemstra, B. (2019). Rational clinical examination of the critically ill patient. Rijksuniversiteit Groningen.

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General introduction and thesis outline

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General introduction

Critically ill patients are admitted to the intensive care unit (ICU) regardless of the underlying pathology or referring specialism. Despite their heterogenous pathologies, all ICU patients require intensive circulatory monitoring due to a high risk of haemodynamic instability or shock, a life-threatening form of acute circulatory failure associated with cellular and tissue hypoxia due to inadequate oxygen utilization.1,2_{Patients with shock have an increased risk of organ failure with}

long-term morbidity or even death.3

Getting insight in circulatory status and cardiac function is important for setting a diagnosis, for prognostication, and to guide decisions on interventions. Caregivers assess a patient’s circulatory status throughout physical and other clinical examinations, as early recognition and treatment of shock may prevent or reverse further deterioration (Figure 1, section A). An important determinant of oxygen delivery is cardiac output, which is the amount of blood the heart pumps through the circulation each minute. The cardiac output is regulated by various mechanisms, all with a common purpose: to maintain a constant perfusion pressure in order to provide organs and tissues with oxygen and to remove metabolic waste products. Impairment of these mechanisms lead to tissue hypoxia and circulatory shock.

Shock is divided in four subtypes, depending on different underlying pathophysiological mechanisms. Distributive shock is the most prevalent (Figure 1, section B) and is characterised by a pathologically decreased peripheral arterial vasomotor tone or intravascular volume due to vasodilation or extravasation of circulating volume. These patients typically present with a high cardiac output. Distributive shock is often caused by sepsis, yet other causes such as anaphylaxis or loss of sympathic tone (i.e., neurogenic shock) result in similar clinical presentations. Patients who suffer from shock caused by one of the other three mechanisms typically present with a low cardiac output and subsequent organ hypoperfusion (Figure 1, section C). Hypovolemic shock is caused by intravascular volume loss due to internal or external fluid loss, cardiogenic shock from cardiac diseases that diminish cardiac pump function (e.g. acute myocardial infarction or heart failure), and obstructive shock from physical obstruction of the great vessels or the heart itself (e.g. pulmonary embolism or cardiac tamponade, respectively).

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CHAPTER 1

Figure 1. Shown is an algorithm for the initial assessment of a patient in shock (Panel A), relative frequencies of the main types of shock (Panel B), and schematic representations of the four main types of shock (Panel C). The algorithm starts with the most common presentation (i.e., arterial hypotension), but hypotension is sometimes minimal or absent. CVP denotes central venous pressure, and SvO₂ mixed venous oxygen saturation. Reproduced with permission from Vincent J, De Backer D. N Engl J Med 2013;369:1726-1734, Copyright Massachusetts Medical Society.

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Thesis outline

The entire process of setting the correct diagnosis, implementing an appropriate intervention, monitoring treatment effect, and eventually improving patient prognosis in a critically ill patient is a complex chain of events. Evidence-based evaluation of such a process with complex time- dependent repeated interactions between diagnosis and treatment requires an approach that includes all three types of research: diagnostic, prognostic and a combination of intervention with prognostic research. This thesis aimed to increase the evidence base of clinical examination as a diagnostic and prognostic tool in critically ill patients.

Current evidence on clinical examination

Clinical examination is the primary test when evaluating a critically ill patient to facilitate clinical decision making and further diagnostic testing. Currently, clinical examination encompasses reviewing medical history, conducting physical examination and interpreting laboratory values, electrocardiograms, and radiography images. Clinical signs indicating circulatory failure, and biochemical and haemodynamic variables consistent with hypoperfusion are recommended for diagnosing shock.1,2_{Despite its frequent use in routine care, the evidence base of clinical}

examination is considered `best practice’.2_{In chapter 2 we made a systematic overview of all}

studies that evaluated the diagnostic accuracy of clinical examination for diagnosing shock.

Designing a cohort to study simple clinical examination findings

Observational studies are often used for diagnostic testing and prognostication. They are considered to come closer to real-life clinical practice than randomised clinical trials (RCTs).8_On

the other hand, the credibility and reproducibily of observational studies has been questioned.9,10

Because observational studies are often published without a preregistered study protocol, it is difficult to judge if conclusions are based on a predefined research question or on a fishing tour.11,12_{To improve transparency, journals are increasingly encouraging researchers to preregister}

their study protocol containing the rationale, hypothesis and study methods.13-15_{Prior to initaiting}

the study, we registered the study protocol of our single centre observational study, the Simple Intensive Care Studies-I (SICS-I). In chapter 3 we described the study design including the research questions, methodology, and characteristics of the patients included. The SICS-I had a focus on clinical examination of the circulation and aimed to include all acutely admitted patients.

Study registration and data collection is followed by a statistical analysis phase. A multitude of decisions are made during this fase, which has been shown to impact results and conclusions.17

Similar to study registration, journals endorsed the prepublications of statistical analysis plans (SAP) to increase reproducibility and transparency on the planned analyses. Chapter 4 presented the recommended content of SAPs for observational studies; these recommendations were adapted from recommendations made for RCTs.18_{We based our SAP on this recommended content, also}

expecting that it may serve as an example document for future SAPs of observational studies.

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CHAPTER 1

The value of clinical examination

Clinical examination has a dual role since it is not only used as a diagnostic tool, but also serves as a trigger for interventions to improve patient prognosis. Clinical signs such as a low blood pressure or low urine output might reflect a poor tissue perfusion, and treatment is started to prevent vital organ damage due to hypoperfusion. A shortcoming in previous studies is that one clinical sign was associated with mortality without information of the other clinical signs or interventions. This conflicts with daily practice because the health care professional observes a broad spectrum of variables, and instigates treatments based on previous findings. In chapter 5 we studied diagnostic accuracy of a protocolised clinical examination to estimate cardiac output. Chapter 6 described which of these clinical examination variables had the strongest associations with mortality.

Interventions on haemodynamics

The prognosis of critically ill patients might improve when an intervention is started at the right trigger point. It is currently unclear which intervention (if any) is most beneficial for critically ill patients at risk of circulatory failure due to cardiac dysfunction. In a series of systematic reviews with meta-analyses, we aim to find which of the drugs used to increase cardiac pump function (i.e. inotrope) has the most potential for improving patient outcome.19-22_{In chapter 7 of this thesis,}

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References

Vincent JL, De Backer D. Circulatory shock. N Engl J Med. 2013;369(18):1726-1734.

Cecconi M, De Backer D, Antonelli M, et al. Consensus on circulatory shock and hemodynamic monitoring. task force of the european society of intensive care medicine. Intensive Care Med. 2014;40(12):1795-1815. Vincent JL, Marshall JC, Namendys-Silva SA, et al. Assessment of the worldwide burden of critical illness: The intensive care over nations (ICON) audit. Lancet Respir Med. 2014;2(5):380-386.

De Backer D, Biston P, Devriendt J, et al. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med. 2010;362(9):779-789.

Kouraki K, Schneider S, Uebis R, et al. Characteristics and clinical outcome of 458 patients with acute myocardial infarction requiring mechanical ventilation. results of the BEAT registry of the ALKK-study group. Clin Res Cardiol. 2011;100(3):235-239.

Lazzeri C, Valente S, Chiostri M, Attana P, Mattesini A, Gensini GF. Mechanical ventilation in the early phase of ST elevation myocardial infarction treated with mechanical revascularization. Cardiol J. 2013;20(6):612- 617. Berdowski J, Berg RA, Tijssen JG, Koster RW. Global incidences of out-of-hospital cardiac arrest and survival rates: Systematic review of 67 prospective studies. Resuscitation. 2010;81(11):1479-1487. Dal-Re R, Ioannidis JP, Bracken MB, et al. Making prospective registration of observational research a reality. Sci Transl Med. 2014;6(224):224cm1.

Ioannidis JP. Why most published research findings are false. PLoS Med. 2005;2(8):e124.

Ioannidis JP. Why most discovered true associations are inflated. Epidemiology. 2008;19(5):640-648. Bracken MB. Preregistration of epidemiology protocols: A commentary in support. Epidemiology. 2011;22(2):135-137.

Ioannidis JP. The importance of potential studies that have not existed and registration of observational data sets. JAMA. 2012;308(6):575-576.

Loder E, Groves T, Macauley D. Registration of observational studies. BMJ. 2010;340:c950. The Lancet. Should protocols for observational research be registered? Lancet. 2010;375(9712):1. PLOS Medicine Editors. Observational studies: Getting clear about transparency. PLoS Med. 2014;11(8):e1001711.

Chan AW, Tetzlaff JM, Altman DG, et al. SPIRIT 2013 statement: Defining standard protocol items for clinical trials. Ann Intern Med. 2013;158(3):200-207.

Ebrahim S, Sohani ZN, Montoya L, et al. Reanalyses of randomized clinical trial data. JAMA. 2014;312(10):1024-1032.

Gamble C, Krishan A, Stocken D, et al. Guidelines for the content of statistical analysis plans in clinical trials. JAMA. 2017;318(23):2337-2343.

Koster G, Wetterslev J, Gluud C, et al. Effects of levosimendan for low cardiac output syndrome in critically ill patients: Systematic review with meta-analysis and trial sequential analysis. Intensive Care Med. 2015;41(2):203-221.

Koster G, Bekema HJ, Wetterslev J, Gluud C, Keus F, van der Horst, I C. Milrinone for cardiac dysfunction in critically ill adult patients: A systematic review of randomised clinical trials with meta-analysis and trial sequential analysis. Intensive Care Med. 2016;42(9):1322-1335.

van der Horst I, Keus F, Hiemstra B, Koster G, Wetterslev J, Gluud C. Dopamine for cardiac dysfunction in critically ill adult patients: A systematic review with meta-analysis and trial sequential analysis. PROSPERO 2016: CRD42016042867.

van der Horst I, Keus F, Koster G, Hiemstra B, Wetterslev J, Gluud C. Dobutamine for cardiac dysfunction in critically ill adult patients: A systematic review with meta-analysis and trial sequential analysis. PROSPERO 2016 CRD42016042829. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22

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