Tese de Doutoramento, Medicina, Investigação Clínica, Universidade Nova de Lisboa

The Autonomic Nervous System, functionally composed by the Intrinsic Autonomic Nervous System, Sympathetic Extrinsic Autonomic Nervous System and Parasympathetic Extrinsic Autonomic Nervous System, is one of the most primitive systems that is responsible for the survival of the human species. The harmony of the various organs and systems depends in a large scale on the balance between the various components of the Autonomic Nervous System, as well as their proper interaction with the other systems. There are several methods to test its functioning: cardiovascular autonomic reflex tests, heart rate variability analysis, serum determination of neurotransmitters, microneurography and sudomotor function tests. In clinical practice, it is usual to use the autonomic cardiovascular reflexes, heart rate variability analysis and sudomotor function tests; however, its applicability in patients hospitalized in the Intensive Care setting has been restricted, almost exclusively, to the analysis of heart rate variability; and among the scientific community of Intensive Medicine, a medical specialty with solid foundations in pathophysiology, the Autonomic Nervous System has been kept out of the scientific interest of its professionals. Doubt is legitimate: is it not an intellectually stimulating subject, or is it not appropriate for clinical practice? In the chapter "Study of the Autonomic Nervous System in Intensive Care Environment - State of the art" a critical review of the literature on the applicability of its monitoring in critical patients is made. This review concludes that studying the correlation between heart rate variability and prognosis is the focus, and all studies indicate that lower the heart rate variability, worse the prognosis. There are also some studies on the blood pressure variability, namely studying the baroreflex, once again the focus is on the prognosis, presenting worse prognosis the patients with low baroreflex sensitivity. Pupillometry and pupil light response is an exception to the previous scenario, since it is used as a tool to titrate analgesia in critical patients and to infer changes in intracranial pressure; it is also used as a prognostic tool in patients suffering from cerebral anoxia and in non-convulsive status epilepticus. Focusing the studies in evaluation the Autonomic Nervous System as a prognostic tool, without direct clinical applicability to modify the outcome of the patients, may be one of the limiting factors for its introduction as a monitoring instrument in the daily clinical practice of the Intensive Care Units. The chapter "Monitoring the Autonomic Nervous System in an Intensive Care environment as a prognostic tool. Systematic review "emerged as a natural need for previously developed work. Considering the multiple studies that addressed the evaluation of heart rate variability, there was a need for a systematic review of the studies, to evaluate if the results were consistent. All studies published in intensive care settings are cohort, prospective or retrospective, focusing on trauma, severe sepsis and septic shock, multiorgan dysfunction, cardiorespiratory arrest, stroke and neurosurgical patients; regardless of the variables studied, it was unanimous that heart rate variability is inversely related with clinical severity and prognosis. After finishing the previous chapter, some methodological doubts emerged: there is no standardization of the variables studied, nor of the methods, and there is almost no application of the time-frequency methods in patients hospitalized in intensive care units. The chapter "Evaluation of the Autonomic Nervous System by monitoring the heart rate variability in Intensive Care environment. Comparison of methods" try to answer those questions. Heart rate variability was studied in time domain, in frequency domain (Welch method, autoregressive model and Lomd-Scargle method) and in timefrequency domain (Burg method, Lomb-Scargle method, Wavelet transform and Hilbert- Huang transform) in 324 blocks of electrocardiographic stable signal, obtained in 82 patients. Strong and very strong correlations were identified between variables in the time domain and variables in the frequency domain, these same correlations were replicated with the variables in the time-frequency domain. Despite the very strong positive correlation between the various methods and models available to study the Autonomic Nervous System balance, there was no concordance between them, which reinforces the need to standardize the methodology of Autonomic study. During collection and treatment of data for the previous chapter, it was found that, in some patients there was an underestimation of the power of the HF band, because patients admitted to the Intensive Care Unit had higher respiratory rate values. Respiratory frequencies above 24 cpm are outside the upper limit of the HF band spectrum and are therefore not quantified. This observation originated a short chapter entitled "Variability of heart rate. The spectrum of high frequency bands is not suitable for all adult patients admitted in Intensive Care. The chapter "Valsalva maneuver. A new proposal for its use in patients submitted to mechanical ventilation" has the objective to transform the Autonomic Nervous System monitoring into a useful instrument for therapeutic orientation in Intensive Care patients with hemodynamic instability. A small pilot study was performed, to adapt the Valsalva maneuver during the inspiratory pause maneuver in patients submitted to mechanical ventilation. Despite the small number of observations presented, it can be stated that the Valsalva maneuver is replicable in these patients and there is a concordance of the continuous Autonomic Nervous System monitoring with the various phases of the maneuver, namely in the vagal, a and b-adrenergic modulation. Lastly, and to highlight the importance of the introduction of the continuous Autonomic Nervous System monitoring in Intensive Care Units, through the methods of timefrequency domain, I present the chapter "Monitoring of events". In this chapter, observation the adaptive response of the Autonomic Nervous System when exposed to short-term phenomena, like vasoactive syringes exchange, coughing and tracheal aspiration, may indicate its balance and, if necessary, what measures to take.