Background: Variations of heart cycles reflect complex dynamic cardiocirculatory regulatory systems in humans. Exposure to tobacco from cigarettes has been shown to elicit specific alterations of heart rate variability parameters leading to predominance of sympathetic and decreasing parameters of parasympathetic measures of cardiac autonomic nervous system tone. Aim: The aim of the trial was assessing differences of linear parameters of heart rate variability in subjects with habit of consuming of cigarettes tobacco in regard to subjects who are not consumers of tobacco. Methods: Patients of ASA II class with border-line arterial hypertension planned for elective abdominal surgery were included in the clinical trial. Twenty-two subjects were allocated to group I, with history of smoking twenty or more cigarettes per day for five or more years, and twenty-three subjects nonsmokers were allocated to group II. Recordings of electrocardiogram were done by Holter device and later on short- term heart rate variability (five minutes periods) were analyzed. Parameters of time domain analysis (SDNN-standard deviation of NN intervals, mean RR interval, mean heart rate) and frequency domain measures (low frequency (LF), high frequency (HF), and LF/HF ratio) were analyzed. Results: Baseline measures of mean NN intervals and standard deviation of normal to normal interval (SDNN) were slightly lower in subjects consumers of nicotine by cigarette tobacco smoking in regard to nonsmokers but without significant difference (640+-15ms vs 675+-8ms, p<0.1;45,1+-3,4 ms vs 51,4+ 3,7ms, p<0.08, respectively). Values of frequency domain measures (LF, HF and LF/HF ratio) have shown variations between two groups, but no significant difference was found.

Introduction: Heart rate variability which denotes variations of the length of consecutive heart cycles has been suggested to reflect the modulation of heart rate by autonomic nervous system. Methods: Sixty four patients of ASA I and ASA II status scheduled for elective abdominal surgical procedures were randomly allocated to group 1 and group 2. Premedication and induction of anaesthesia were performed with same agents. After orotracheal intubation maintenance of balanced anaesthesia was based on administration of same induction agents,opioids and muscle relaxant while delivery of gaseous mixture with sevoflurane in the group 1 (n=32) and isoflurane in the group 2(n=32). Haemodynamic parameters were monitored in perioperative and electrocardiogram was recorded by holter ECG recorder, while the analysis of the parameters were performed by corresponding softwares . Data were presented as mean values of logarithmic (natural logarithm) values of the power of the total spectrum of heart rate variability(TP), mean values of the logarithmic values of low frequency band (LF), mean values of the logarithmic values of high frequency range(HF), and mean values of SD1 and SD2 parameters. Results: Analysis of the values of hemodynamic parameters has shown changes of haemodynamic parameters during perioperative period without significant statistical differences between the groups. Analysis of the logarhitmic values of parameters of heart rate variability of frequency domain has shown changes of the total spectrum power and LF and HF spestra with variations of the values of total power spectrum and individual components of the spectrum of heart rate variability during the balanced anaesthesia with administration of two different inhalation anaesthetics, without statistically significant differences between the groups. Conclusion: The results have shown that during balanced anaesthesia with two different inhalation anaesthetics there are variations of haemodynamic variables and parameters of heart rate variability without statistically significance that could show the difference between the groups and different agents administered.

Assessment of the autonomic nervous system function could be of great importance in evaluation of the risk factors of the patients in perioperative period. Surgery and anaesthesia as integral medical procedures aimed as restoring and improving different disorders of homoestasis and physical conditions of subjects with different ailments and functional cardiac reserves have strong influence on haemodynamic function in perioperative period and it is of a great importance to clearly define if an individual patient is at a great risk of autonomic dysfunction in addition to the underlying morbidity, whicht increase the risk of morbidity and mortality in the perioperative period. Clinical tests for evaluation of autonomic nervous dysfunction have not become widely used by clinicians for several reasons. Some of the clinical tests are quite demanding what makes them less possible for performing in patients with poor reserve and more comorbidities and there are also difficulties in interpretation of subjective findings. Monitoring of heart rate variability as a parameter of autonomic nervous system activity has been clearly advocated in the risk assessment and follow up of the patients who develop diabetes mellitus and patients with coronary syndrome [1]. In subjects with diabetes mellitus who could have cardiac autonomic diabetic neuropathy, the quite serious condition of haemodynamic instability could increase the risk of aggravation and complications of the general condition in perioperative period [2]. On the other hand, most subjects with different stages of coronary syndrome have been shown to have different alterations of heart rate variability, and monitoring of heart rate viability in perioperative period could be a part of predicting tools of risk factors for surgery and anaesthesia [3]. The aim of this paper to give a reviewi of the importance of assessment of heart rate variability in relatively healthy subjects and subjects with different comorbid states, focusing on presenting of different findings of linear meaures of the analysis of parameter by means of two different softwares. Figure 1. Tachogram during calm and deep respiration in relatively healthy subject

E-mail: meldi@bih.net.ba Heart rate variability, a phenomenon of variations of the length of consecutive heat cycles reflects the autonomic modulation of the heart function. Parameters of monitoring the heart rate variability are suggested to be important in the assessment of autonomic neuropathy that may complicate several pathological conditions, with established clinical importance in predicting morbidity and mortality in patients with coronary syndrome and in patients with diabetes mellitus. The complexity of the critical illness of the subjects in the intensive care unit demands complex pharmacological and procedural therapeutic interventions and measures, which all have a significant impact on the parameters of heart rate variability. Such complex interactions limit the possibility to reach conclusions on a potential degree of the influences of the deteriorated organ function and the influence of the therapeutic interventions. Despite difficulties and limitations of interpretation of the variations and depression of the heart rate variability parameters, research in this field has been continuing. In this paper, different parameters of short-term heart rate variability monitored in 25 consecutive patients who were admitted to an adult intensive care medicine unit for different conditions of critical illness are presented.

INTRODUCTION Alterations of the parameters of heart rate variability, phenomenon associated with autonomic nervous system balance, have been shown as a possibly very important factor for monitoring of cardiocirculatory system in the perioperative period. Periinduction period of general anaesthesia is very important with significant changes of haemodynamics what could be reflected in the changes of the parameter of heart rate variability. METHODS A hundred patients of ASA I and ASA II status who were scheduled for elective abdominal surgical procedures of moderate stress response, were randomly assigned to group I and group II, who were administered propofol or thiopentone as induction anaesthetic, respectively. Monitoring during periinduction period included of monitoring of mean blood pressure (noninvasively), heart rate, pulseoxymetry and recording of electrocardiogram by holter ECG recorder for further analysis of heart rate variability, in four time segments in periinduction period: Tp, T1, T2, T3. Data were presented as mean values of absolute values of the power of the total spectrum of heart rate variability, mean values of the spectrum of low frequency band (LF), mean values of the high frequency range, and the ratio LF/HF. RESULTS Analysis of the values of hemodynamic parameters has shown decrease of mean arterial blood pressure after induction of anaesthesia with intravenous anesthetics thiopental or propofol, with simultaneous changes of heart rate in the four time segments in periinduction period, without statistically significant changes between the groups. Analysis of the values of parameters of heart rate variability measured in the frequency domain has shown changes of mean values of the absolute values of total power spectrum, mean values of the power of low frequency spectrum and mean values of the power of high power spectrum with reduction of the values of total power spectrum, the power of low frequency spectrum and the power of high frequency spectrum, most pronounced just after induction of anaesthesia with slight increase of the values of total power spectrum and individual components of the spectrum of heart rate variability in the later postinduction period, without statistically significant differences between the groups. CONCLUSION The results have shown that in the groups of patients who underwent induction of general anaesthesia with propofol or thiopentone, there have been reductions of the total spectral power and the power of the spectrum of low frequency components and high frequency components with variations in the relationship between the components in the different periods of periinduction time.

Monitoring of changes in heart rate is the commonest way of rapid assessment of cardiovascular function in everyday clinical practice. Analysis of the recordings of the heart electrical activity enabled the discovery that specific fluctuations of the length of consecutive heart cycles, which can not be measured in clinical examination, are associated with physiological conditions. That phenomenon, named heart rate variability, could be evaluated only by implementing special measurements, based on time domain analysis and frequency domain analysis which give many parameters that are related to the functioning of two branches of autonomous nervous system: sympathetic and parasympathetic system. Many observational and controlled clinical studies have shown reduced heart rate variability in different pathological conditions, so that it could be a useful tool in risk stratification after acute myocardial infarction, or coronary artery disease, in diabetic autonomic neuropathy, endocrine diseases, neurologic and psychiatric diseases. During anaesthesia, there are profound alterations in autonomic nervous tone, depending on the comorbidity and the agents that are used for induction and maintenance. Measurements of changes in autonomic function is very important, and could give a possibility for determination of the perioperative risk and timely correction of the dysfunction, especially in high risk patients. Some aspects of measurement of heart rate variability and changes of the values of parameters in different pathological conditions and in anaesthesia are reviewed.

The practice of evidence based medicine in the setting of intensive care unit is very important part and contributory component of optimal clinical practice. Integration of personal clinical expertise, best available evidence from systematic research and patients’ values and expectations, should be accomplished in order to have the best approach in diagnostics and therapy. There have been many advancements and progress in the treatment of critically ill patients in last decades, with introducing many new techniques of invasive and noninvasive monitoring and appliance of devices and machines that support vital functions and prolong the time which is available for resuscitation and intensive treatment. In the same time conduction of good randomized controlled trials is limited because of ethical issues, complicated procedures and different protocols of care, ambiguous definitions of diseases and syndromes, and results that sometimes could not be translated in practice. Despite considerable limitations, many large controlled randomized studies and observational studies have contributed a lot to the clinical expertise, what resulted in changing the practice of intensive care medicine. There is general consensus on the ways of treatment of cardiovascular and respiratory failure, with emphasis on early starting of resuscitation and adapting mechanical ventilation to individual needs of patients. Optimal glycemia levels, levels of haemoglobin, the role of corticosteroid therapy in septic shock will continue to be the issue of future investigations in order to obtain valid recommendations.

In the last decades analysis of heart rate variability has emerged as a new useful tool for assessing the changes in autonomic tone that influences cardiovascular function. High variability of oscillations and the integrated physiologic activities of heart and cardiovascular system isassociated with physiologic functioning. Irregularity of the length of consecutive heart cycles, designated as heart rate variability, reflects the ability of cardiovascular system to adapt to different situations in everyday life. Reduction of these fluctuations of the heart periods has been shown to be associated with pathological conditions in many experimental and clinical trials. The extent and consistency of the reduction of heart rate variability in the patients after acute coronary events, were shown to be related to mortality and cardiovascular dysfunction. In patients with diabetes mellitus who develop autonomic neuropathy, reduced heart rate variability is quite common. Reduced heart rate variability was shown in endocrine disorders, neurological and psychiatric diseases, with use of different drugs and many other conditions. The most common ways of measuring heart rate variability are measuring in time domain analysis and frequency domain analysis. Parameters calculated from the measurements are related to the functions of sympathetic and parasympathetic nervous system. Measurements of changes in autonomic function is very important in the follow up in different diseases and for determination of the efficacy of the therapy. In the field of surgery and anaesthesia, besides preoperative risk stratification, there are many studies on the effects of different anaesthetics on heart rate variability. In this paper, some aspects of measurement of heart rate variability and changes of the values of parameters in different pathological conditions and clinical implications are reviewed.

Neurologic complications after severe brain injuries are the result of primary injuries in the moment of impact and secondary injuries which evolve over the minutes and days later. According to statistics, secondary injuries were documented in about 90 percent of patients who died after traumatic brain injury. Low oxygen delivery in hypotension, hypoxia, oedema, intracranial hypertension or changes in cerebral blood flow all account for development of secondary injuries. Primary injuries are more or less complete, but secondary injuries could be prevented with adequate therapy. Understanding mechanisms of secondary injuries could help identify potentially beneficial therapies. Important elements of therapy are: head position, normoglycemia, osmotherapy, normal body temperature, optimal blood pressure, adequate oxygenation. barbiturate therapy. Neutral head and neck position is recommended to prevent intracranial hypertension. Hyperglycemia with less ATP leads to ishaemic acidosis, hypoglycemia enhances decomposition of phospholipids and release of fat acids, what makes the celulare damage worse. Normocapnia is recommended and adequate oxygenation (PaO2 higher than 90%). To prevent dehydration and electrolyte imbalance, serum electrolytes should be examined every 4-6 h as well as osmolarity. Moderate therapeutic hypothermia could be of benefit, and maintaining of optimal blood pressure (MAP above 90 mmHg), especiallz in the first period after injury. As thez have a lot of adverse effects, barbiturates are recommended only when conventional therapies show no effect. Patients should be hydrated well before induction of barbiturates. In organized trauma centers and with adequate intensive care the mortality from traumatic brain injury decreased from 50% in 1970, to about 30% nowdays.

Malnutrition is very common in critically ill patients. According to the available data, a high percentage of patients (30-60%) suffers from some degree of malnutrition, and in 10-15% of patients malnutrition can be very severe. Patient's nutritional status usually worsens during hospitalization. In malnutrition, the functions of all organ systems change. Surgical treatment is a stress for the body, which leads to the predominant catabolic response with accelerated decomposition of the non-fat tissue, resulting in enhanced gluconeogenesis and negative nitrogen balance, which further compromise body's vital functions. Due to such physiological effects, malnutrition is followed by increased number of complications of the underlying disease, higher mortality rate, prolonged hospitalization and increased treatment costs. Malnutrition is common in clinical practice, so at the time of the admission, all patients should be checked for signs of malnutrition. After noticing the presence of the increased risk, it is necessary to make a plan for preoperative nutritional support, in order to prepare the patient optimally for the surgical procedure. It is also necessary to check the factors which might lead to further worsening of the nutritional status of the patient. With adequate screening and therapy, it is possible to improve patients' general condition and the outcome, as well as to reduce the percentage of complications, mortality rate and treatment costs.

Neurologic complications after severe brain injuries are the result of primary injuries in the moment of impact and secondary injuries which evolve over the minutes and days later. According to statistics, secondary injuries were documented in about 90 percent of patients who died after traumatic brain injury. Low oxygen delivery in hypotension, hypoxia, oedema, intracranial hypertension or changes in cerebral blood flow all account for development of secondary injuries. Primary injuries are more or less complete, but secondary injuries could be prevented with adequate therapy. Understanding mechanisms of secondary injuries could help identify potentially beneficial therapies. Important elements of therapy are: head position, normoglycemia, osmotherapy, normal body temperature, optimal blood pressure, adequate oxygenation, barbiturate therapy. Neutral head and neck position is recommended to prevent intracranial hypertension. Hyperglycemia with less ATP leads to ishaemic acidosis, hypoglycemia enhances decomposition of phospholipids and release of fat acids, what makes the cellular damage worse. Normocapnia is recommended and adequate oxygenation (PaO2 higher than 90%). To prevent dehydration and electrolyte imbalance, serum electrolytes should be examined every 4-6 h as well as osmolarity. Moderate therapeutic hypothermia could be of benefit, and maintaining of optimal blood pressure (MAP above 90 mmHg), especially in the first period after injury. As these have a lot of adverse effects, barbiturates are recommended only when conventional therapies show no effect. Patients should be hydrated well before induction of barbiturates. In organized trauma centers and with adequate intensive care the mortality from traumatic brain injury decreased from 50% in 1970, to about 30% now days.