CC BY
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EFFECTS OF SEDATION WITH MODERN A-2 AGONISTS ON PERIOPERATIVE PERIOD IN GENERAL
SURGERY PATIENTS
Domoratsky A. E., Krylyuk V. O., Sozansky V. V.
Rybak K. A., Kryatchenko E. B., Beisiuk O. D.
National Medical Academy of Postgraduate Education named after P. L. Shupyk.
Kyiv City Clinical Hospital ambulance
Abstract. a-2 agonists have a number of useful pharmacodynamic effects such as anxiolytic, sympatholytic, antinociceptive. They are very useful in the practice of anesthesia. On the other hand, their use is limited by side effects: severe hypotension and bradycardia, especially in their interaction with anesthetics. Nowadays in Ukraine are available - a long time known clonidine and deksmedetomedin - modern a-2 agonist. We learned the efficiency and safety of sedation by deksmedetomedin at a dose of 0.7 mcg / kg. Demonstrated positive effects of using deksmedetomedin in patients with acute abdominal surgical pathology.
Keywords: a-2 agonists, deksmedetomedin, premedication, Deksdor.
Relevance.
Traditionally, anesthesiologists use specific drugs to ensure proper condition of the patient prior to anesthesia in the clinic. The goal of sedation is to ensure reduction of patients anxiety, providing of amnesia and analgesia, vagolytic effect, reduction of exocrine secretion, prevention of aspiration of acidic gastric contents, postoperative nausea and vomiting, decreasing needs of analgesics in the perioperative period. For this purpose, we traditionally use the psychological preparation of the patient and many groups of pharmacological agents, such as benzodiazepines, m-anticholinergic antagonists of serotonin receptors, steroids, non-steroidal anti-inflammatory drugs and others. Premedication is held on the eve of surgery and directly 20 - 30 minutes before the start of the operation ("on the table"). In urgent cases, the preparation for the operation is limited in time and accompanied by a lot of stress for both the patient and medical staff.
The group of a-2 agonists has an interest in their use in various stages of perioperative period for decades. At the present moment in Ukraine are available two kinds of drugs: Clonidine and dexmedetomidine (Dexdor). The relevance of a-2 agonists use caused by beneficial effects such as a central sympatholytic effects, sedation, anxiolysis, analgesia, decrease the secretion of the salivary glands, prolongation of action of local anesthetics and opioids. [1,2,3] The data obtained the reduction of adverse effects from the cardiovascular system in high cardiac risk patients after noncardiac operations after applying a-2 agonists. [4,5]. Also, the use of deksmedetomedin reduces the incidence of postoperative delirium and cases of delirium in ICU patients on mechanical ventilation. [6,7]. The use of clonidine in premedication "on the table" is limited by the severity of adverse cardiovascular effects such as hypotension and bradycardia. The Dexdor may have these possible reactions, but they are less expressed. Clonidine has established itself as the i$ay and effective adjuvant for regional anesthesia. [8,9] It is worth noting that the US company that manufactures deksmedetomedine (Presideks) allowed it for epidural and intrathecal administration, this function is "off-label" for our country.
Materials and methods
The research was conducted on the basis of the intensive care unit of the Kyiv municipal clinical emergency hospital. The study included 47 patients, where women accounted for 61,7% (n = 29) and men 38,3% (n = 18). All informing patients consent was obtained. Performed operations: appendectomy, laparoscopic cholecystectomy, removal of the intestinal obstruction. Were excluded
patients under 18 and more than 60 years old, patients with traumatic brain injury history, any surgery under general anesthesia, patients with ASA risk more than 2, and patients with a body mass index higher than 35.
All patients were provided by total intravenous anesthesia (TIVA) with standard doses of sodium thiopental, fentanyl, succinylcholine, atracurium. All patients routinely, before sedation, were administered by balanced crystalloid solution preinfusion in the amount of 6 - 8 mL / kg . Dexmedetomedine (Dexdor) was used as premedication drug "on the table". Premedication "on the table" was conducted 30 minutes before the start of the operation. Dexmedetomedine administered via infusomates for 20 minutes, also was routinely prescribed premedication with ondansetron (Osetron) 4mg i.v. and dexketoprofen (Deksalgin) 50 mg. i.m.
The patient in the perioperative period was held the next monitoring: history, the objective of all organs and systems, general analysis of blood, electrocardiography, blood chemistry, urinalysis, non-invasive blood pressure (BP) every 5 minutes (systolic, diastolic, mean), continuous pulse oximetry using the UTAS system, sedation was evaluated by the Richmond agitation-sedation scale (RAAS), postoperative recovery scale (PRS). The obtained results were subject to the normal distribution, in the processing using traditional methods of parametric statistics. Analysis using STATISTICA 6.0 software (Statsoft Inc. 2001).
Results and discussion
The recommended doses of Dexdor for sedation ranges from 0.2 to 1.2 mg / kg / hour. Starting dose for sedation of ventilated patients 0.7 mcg / kg / hour, the recommended dose for more rapid onset of sedation - 0.5 - 1.0 mg / kg for 20 minutes, which make up 1.5 - 3 mcg / h. Considering the lack of experience of deksmedetomedine use in anesthesiology and inevitable summation effects from medications for total intravenous anesthesia (TIVA), it was decided to find out the most effective and secure premedication dose. For this purpose, a series of empirical observations of 30 cases was carried out. Dexmedetomedine was administered to the patients in doses of 0.2 to 1.0 mcg / kg / min in 20 minutes. Afterwards, the patient's condition was monitored and interviewed both patients and anesthesiologists who provided anestesia. While introducing dose of dexmedetomidine was 0.2 - 0.4 mcg / kg patients noted absence of sedation or anxiolysis, doctors did not report changes in anesthetics and analgesics doses, and observed no side effects. In the dose of dexmedetomidine 0.5 -0.8 mcg / kg patients reported anxiolysis, but maintained contact with the medical staff (estimated at RAAS 0, -1), doctors noted an improvement in the contact with the patient, intraoperative decrease of analgesics dose, minimum unwanted effects. In the range of 0.9 - 1.0 mg / kg patients reported drowsiness (RAAS -1, -3), doctors have noted a decrease in analgesic requirements, bradycardia which required atropine correction, longer awakening after surgery. In all cases, the vital functions were not violated. There was not a single case of adverse effects in the postoperative period. It should be noted the reluctance of physicians to use more than routine premedication dose higher than 0.8 mcg / kg. In a further study routinely was used dosage of 0.7 mcg / kg for 20 minutes, which is equal 2.1 mcg / kg per hour.
Table 1. Clinical characteristics of the group
Feature Value
Age, years 44,83 ± 2,55
Height, cm 171,59 ± 2,86
Weight, kg 79,5 ± 4,2
ASA I/II/n 26/21
The duration of surgery, min 81,92 ± 7,84
extubation time, from the end of surgery, min 23,25 ± 2,73
Dexmedetomidine dose ,mcg 55,76 ± 2,61
Table 2. The effectiveness of dexmedetomidine premedication
RAAS Score Before premedication, n/% After premedication, n /%
+ 2 5/10,63 0
+ 1 33/70,21 8/17,02
0 9/19,14 22/46,80
- 1 0 11/23,4
- 2 0 7/14,89
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Premedication with dexmedetomidine proved its effectiveness. It should be noted that 70.1% of the patients had 0 - (-1) point by RAAS. In the occurrence of anxiolysis, there was no notable sedation and the patient maintained contact with the medical staff. Subjectively, patients noted a relaxation, reducing of the "internal tremor" and assessed his condition as "mild."
Table 3. Safety of dexmedetomidine premedication
Index Before premedication Induction of anesthesia The main stage of surgery The End of surgery After extubation
systBP mm, Hg 148 ± 4,72* 126,25 ± 3,05* 125 ± 2,46 124,09 ±2,54 127,04 ± 2,33
liastBP mm, Hg 90,8 ± 2,7* 77,08 ± 1,9* 79,09 ± 2,28 79,77 ± 2,31 80,4 ± 2,29
MAP mm, Hg 110,48 ± 3,11* 94,79 ± 2,1* 94,09 ± 1,86 94,31±1,96 95,59 ± 1,91
HR, bpm 83,68 ± 2,09* 70,25 ± 1,73* 70,09 ± 1,77 71,27 ± 1,77 73,27 ± 1,46
* p < 0,01
All a-2 agonists have adverse effects on the cardiovascular system, which include hypotension and bradycardia, decreasing in stroke volume and cardiac output. Although the manufacturer describes hypotension and bradycardia, as a very common adverse reactions (for sedation in the ICU, we noted a significant decline in blood pressure and heart rate after Dexdor infusion (p <0.01), but we have observed no cases of hypotension, which would require medical correction. The lack of significant difference of hemodynamic parameters after extubation with the same intraoperative criteria indicates the absence of the pressor response to extubation. However, we have observed two cases of bradycardia (heart rate 42) at the end of infusion of dexmedetomidine, and heart rate 48 fifteen minutes after the start of the operation. Both cases were easily corrected by injection of atropine 0.5 mg that was not routinely used for the premedication. We also observed two urgent patients with blood pressure 180/100 mm Hg, in which blood pressure dropped to 150/90 and 140/90 mm Hg after infusion of Dexdor. Further, we did not observe a tendency to hypotension. Biochemical parameters were within the reference values after 12 and 72 hours. We assume that premedication with dexmedetomidine does not lead to hypo / hyperglycemia, despite manufacturer describes these adverse reactions as frequent (for sedation in the ICU).
We analyzed the need for anesthetic agents. In the group of patients who were premedicated with Dexdor, the average amount of fentanyl was 715.21 ± 90.9 mcg (about 7, 95 mcg / kg / hour), thiopental Na 985,21 ± 93, 66 mg. The obtained data were compared with the retrospective group, in which diazepam (Sibazon) was used for premedication. We composed the retrospective group that was comparable to the clinical study group (n = 50), where the average amount of spent fentanyl was 910,42 ± 92,2 (10,1 mcg / kg / hour), thiopental Na 1152 ± 91,22 mg. The analysis showed a significant decrease of spent fentanyl (p <0.05). Reduction in the total dose of thiopental Na was not significant. The authors assume that it is early to make an unambiguous conclusion about the analgesics dose reduction during TIVA after using dexmedetomidine, but there is a tendency that needs further studies. Also, it should be noted that there were no cases of postoperative shivering.
Subjectively, the authors noted that the positive effects of premedication with dexmedetomidine are more noticeable if the duration of the operation does not exceed 80 - 90 minutes. The authors have recorded a longer time needed for extubation and associate it with the interaction of anesthetics with a-2 agonist and an appropriate adaptation of the patient to the ventilator. The most noticeable delay of extubation was observed in cases of short surgical interventions about 20 - 30 minutes.
Conclusions
Certainly, preparing of a patient for the planned, and especially for the urgent surgical intervention is an actual issue of modern anesthesiology. Dexmedetomidine has shown its effectiveness to achieve anxiolysis, and as a result, decreasing the body's reaction to stress. All patients notice easy tolerance of the medication. Receiving of Dexdor infusions in dose 0.7 mg/kg within 20 minutes does not cause adverse effects on the cardiovascular system. Cases of bradycardia are easily corrected by atropine. Of course for the final conclusions, further studies including large groups of patients are needed. Evidently, the use of modern alpha-2 agonists in anesthesiology is promising.
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4. Chalikonda SA Alpha2-adrenergic agonists and their role in the prevention of perioperative adverse cardiac events.// AANA J. - 2009 - Vol. 77 - №2 - Р. 103 - 108.
5. Wijeysundera DN, Bender JS, Beattie WS. Alpha-2 adrenergic agonists for the prevention of cardiac complications among patients undergoing surgery.// Cochrane Database Syst Rev. - 2009 -Vol. 7 - №4 doi: 10.1002/14651858.CD004126.pub2.
6. Chevrolet J.C., Jolliet P. Clinical review: agitation and delirium in the critically ill— significance and management.// Сп1 Care. - 2007 - Vol. 11 - №3 - Р. 214 - 218.
7. Pandharipande P.P., Pun B.T., Herr D.L., Maze M., Girard T.D., Miller R.R., Shintani A.K., Thompson J.L., Jackson J.C., Deppen S.A., Stiles R.A., Dittus R.S., Bernard G.R., Ely E.W. Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. // JAMA. - 2007 - Vol. 298 - №22 - Р. 2644 - 2653.
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THE FREQUENCY OF COMORBID CONDITIONS IN PATIENTS WITH HYPERTENSION
1MD Kuzminova N. V.
1Gribenyuk O. V.
1Romanova V. O.
1MD Osovska N. Y.
2MD Knyazkova 1.1.
Ukraine, Vinnitsa, Vinnitsa National Medial University named after M. Pyrogov, Department of
Internal Medicine No1
2Ukraine, Kharkiv, Kharkiv National Medical University, Department of Clinical Pharmacology
Abstract. Today, weight gain is considered to be not only an important factor in the development and progression of hypertension, but also in the development of nonalcoholic fatty liver disease. According to the results of the examination of 170 patients with stage II hypertension, optimal body weight was observed only in 30 patients (17.6%), overweight - in 37 patients (21.7%), first degree obesity - in 58 (34.1%), second degree obesity - in 45 patients (26.5%). Abdominal fat distribution type predominated in more than 80% of patients with hypertension. The signs of nonalcoholic fatty liver disease, such as steatosis, were registered in 109 (64.1%) patients, its incidence progressively increasing together with body weight gain (from 40.0 % of patients with an optimal body weight and 54.1% of patients with overweight to 65.5% ofpatients with the 1st degree obesity and up to 86.7% of the 2nd degree obesity patients (p<0.05 compared to patients with optimal weight and overweight). Thus, this study demonstrated overweight, 1st and 2nd degrees obesity, to occur in the vast majority of patients with stage II essential hypertension. The frequency of hepatic steatosis increased with the increase in body mass index.
Keywords: hepatic steatosis, hypertension, optimal body weight, overweight, obesity.
Introduction. Today, weight gain plays an important role not only in the development and progression of cardiovascular diseases, but also in the development of the nonalcoholic fatty liver disease (NAFLD) [1]. Comorbidity of liver disease and hypertension often occurs as a part of metabolic syndrome (MS). Obesity, especially, abdominal type, insulin resistance and compensatory
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