Quality and Safety of General Anesthesia with Propofol and Sevoflurane in Children Aged 1-14 Based on Laboratory Parameters

Abstract

Introduction: Knowledge of anatomic, physiological, biochemical and physical characteristics of children of all age groups, the existing illness and possible pathological response of the organism to the existing situation, require a pediatric anesthesiologist to participate in the preparation of a child for surgical treatment, to choose the best anesthesia technique and medications, and manipulative techniques to enable the scheduled surgical treatment with minimum anesthesia risks. The aim of this clinical study was to prove reliability and quality of propofol or sevoflurane general anesthesia in children in the age group of 1-14 years from the ASA I group and in the elective surgical treatments in duration of 60 minutes, based on preoperative and postoperative levels of laboratory findings (transaminases, blood sugar, urea and creatinine). Materials and methods: the study included 160 patients randomized in two groups based on different approaches: total intravenous anesthesia was used for the propofol group (n=80) (TIVA) and the inhalation technique was used for the sevoflurane group (n=80). Results: statistical evaluation of the obtained results indicates stability of laboratory findings in the immediate postoperative course (after 24 hours) in respect to the preoperative period. Based on the Mann Whitney test (P), preoperative and postoperative blood sugar levels in the sevoflurane vs. propofol group were P=0.152 vs. 0.021; creatinine levels P=0.113 vs. 0.325; urea levels P= 0.016 vs. 0.900; AST levels P=0,031 vs. 0,268 and ALT levels P=0.021 vs. 0.058. Level of significance was P<0.5. Conclusion: Analysis of the examined laboratory parameters show that propofol and sevoflurane provide full security and quality of general anesthesia in children age group 1-14 years, from the ASA I group. All analyzed laboratory levels in the postoperative course remained in their referential values in both groups of participants.

Quality and Safety of General Anesthesia with Propofol and Sevourane in Children Aged 1-14

ORIGINAL PAPER doi: 10.5455/medarh.2015.69.218-221

Med Arh. 2015 Aug; 69(4): 218-221

Received: June 15th 2015 | Accepted: July 15th 2015

2015 Selma Vanis-Vatrenjak, Amira Mesic, Ines Abdagic, Djenita Mujezinovic, Zlatan ZvizdicThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http:// creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Quality and Safety of General Anesthesia with Propofol and Sevourane in Children Aged 1-14 Based on Laboratory Parameters

Selma Vanis-Vatrenjak1, Amira Mesic1, Ines Abdagic1, Djenita Mujezinovic1, Zlatan Zvizdic2

1Clinic of Anesthesiology and Reanimation, University Clinical Center Sarajevo, Sarajevo, Bosnia and Herzegovina

2Clinic of Pediatric Surgery, University Clinical Center Sarajevo, Sarajevo, Bosnia and Herzegovina

Corresponding author: Selma Vanis Vatrenjak, MD, MSc Clinic of Anesthesiology and Reanimation University Clinical Center Sarajevo Bolnicka 25, 71000 Sarajevo Bosnia and Herzegovina Email: [email protected]

ABSTRACT

Introduction: Knowledge of anatomic, physiological, biochemical and physical characteristics of children of all age groups, the existing illness and possible pathological response of the organism to the existing situation, require a pediatric anesthesiologist to participate in the preparation of a child for surgical treatment, to choose the best anesthesia technique and medications, and manipulative techniques to enable the scheduled surgical treatment with minimum anesthesia risks. The aim of this clinical study was to prove reliability and quality of propofol or sevourane general anesthesia in children in the age group of 1-14 years from the ASA I group and in the elective surgical treatments in duration of 60 minutes, based on preoperative and postoperative levels of laboratory ndings (transaminases, blood sugar, urea and creatinine). Materials and methods: the study included 160 patients randomized in two groups based on dierent approaches: total intravenous anesthesia was used for the propofol group (n=80) (TIVA) and the inhalation technique was used for the sevourane group (n=80). Results: statistical evaluation of the obtained results indicates stability of laboratory ndings in the immediate postoperative course (after 24 hours) in respect to the preoperative period. Based on the Mann Whitney test (P), preoperative and postoperative blood sugar levels in the sevourane vs. propofol group were P=0.152 vs. 0.021; creatinine levels P=0.113 vs. 0.325; urea levels P= 0.016 vs. 0.900; AST levels P=0,031 vs. 0,268 and ALT levels P=0.021 vs. 0.058. Level of signicance was P<0.5. Conclusion: Analysis of the examined laboratory parameters show that propofol and sevourane provide full security and quality of general anesthesia in children age group 1-14 years, from the ASA I group. All analyzed laboratory levels in the postoperative course remained in their referential values in both groups of participants.

Key words: propofol, sevourane, pediatric anesthesia, laboratory values.

1. INTRODUCTION

Propofol and sevourane are intravenous, inhalator anesthetics of a new generation used in our country in the past two decades. At the very beginning both of these hypnotics were used to induce and maintain general anesthesia in adult patients based on recommendations of pharmaceutical companies in charge of their production.Their use in children, especially in those up to 3 years of age, was not recommended given that there was insufficient data and experience on their side eects and reactions to the medications. Propofol is an intravenous anesthetic agent which for its highly positive pharmacological characteristics, except for total intravenous anesthesia (TIVA), can also be used for sedation of patients in the Intensive Care Unit (ICA). When administered in the recommended dosage for anesthesia it has fast eects, a patient is put into sleep in 20-40 seconds, which based on

the eectiveness is almost equal to dosages of thiopen-tone, with propofol being 1.6-1.8 times stronger (1). Its eect is realized via GABAA receptor (2). Propofol is administered intravenously, metabolized in liver and usually eliminated through urine. For inducing and maintenance of general anesthesia along with opioids (analgetic eect is weak and temporary), relaxants and oxygen can also be used (TIVA) or in combination with inhalation sedation (balanced anesthesia) (1, 2, 3). It is quickly and fully metabolized by conjugation in the liver thanks to enzymes and cytochrome P450 in products without any hypnotic or sedated eects, and is eliminated through kidneys.

Based on its chemical composition sevourane is completelyuorinatedmethyl isopropyl ether. It causes sleep via respiratory system, and is subsequently absorbed from alveolus and transferred into the blood stream and by diusion distributed to all tissues. Anesthesia by sevou-

218 Med Arh. 2015 Aug; 69(4): 218-221

Quality and Safety of General Anesthesia with Propofol and Sevourane in Children Aged 1-14

rane starts when adequate partial anesthetic pressure is achieved in the brain tissue, which is in balance with alveolar partial pressure of anesthetic. It is to a large extent eliminated through the respiratory system, and partially through urine in the shape of organic uoride metabolites (3, 4, 5).

In a study on general intravenous anesthesia by propofol and standard practice in pediatric anesthesia, Strauss JM et al. do not save words of praise for quality, efficiency, hemodynamic stability and minimal side eects during general anesthesia, but they also emphasize and emphasized great caution and experience in work with propofol and total intravenous anesthesia in children (6). A study of Suzuki KS et al. from 2002 and a study of Kamal AH et al, compared the time from inducing anesthesia and waking up from general anesthesia (sevourane in comparison with propofol) and reached identical conclusion as in the previously cited study regarding patients treated with sevourane, emphasizing minimal incidence in the postoperative complications (laryngospasm, stridor, nausea and vomiting) in the same group of patients (7). A study of Shmit J et al. performed on 120 childrenin infant and preschool age divided in two groups, propofol and sevourane, showed higher hemodynamic stability in patients treated with propofol (8). We did not nd any special studies related to analysis of preoperative and postoperative laboratory ndings which we could use for the purpose of comparison. The aim of this clinical study was to prove the reliability and quality of general anesthesia by propofol and sevourane in children of the age group 1-14 years, ASA I group, and in pre elective 60 minute surgery based on preoperative and postoperative values of laboratory ndings (transaminases, blood sugar, urea and creatinine).

2. MATERIALS AND METHODS

Our country has not conducted any investigation aimed towards the comparison of preoperative and immediate postoperative laboratory parameters in propofol and sevourane anesthesia in children age group 1-14 years and ASA I group. This is a prospective, descriptive, randomized clinical study. The study was public and conducted with strict adherence to the requirements of ethics and humanity in accordance with the Helsinki declaration.

The inclusive criteria were as follows: patients from 1 to 14 years of age (n=160) hospitalized at the Pediatric Surgery of the University Clinical Center Sarajevo (UCCS) for the purpose of elective surgery; patients who based on the local report of a pediatric surgeon were indicated for surgery; patients with pediatric report and a surgery consent of a pediatrician; patients from ASA I group; patients with clinical diagnosis whose parents provided full data in the anamnesis questionnaire; patients with all laboratory parameters required for this study; patients whose parents gave consent for surgery; patients pre-medicated according to the established plan. Patients data and values measured during the study were recorded in a specially designed form.

In the propofol group of patients, opioid fentanyl was administer at a dose of 0.005 mg/kg, followed by a muscle relaxant vecuronium-bromide 10 minutes later at a dose

of 0.1 mg/kg. After administration of the muscle relaxant an intravenous propofol bolus doze of 3 mg/kg was immediately administered. During the administration of opioid, muscle relaxant and propofol, all patients from the propofol group received oxygen via anesthetic oxygen mask in the amount of 5 l/h. After achieving the state of sleep and muscle relaxation the patients were intubated with an appropriate size endotracheal tube. Continuous ventilation was achieved mechanically via anesthetic apparatus IPPV (Intermittent positive pressure ventilation). Tidal volume (breathing volume) and the respiration rate were adjusted to the age and weight of a child. The rate of inhaled gases during anesthesia was adjusted as follows: oxygen/ nitrogen oxide 50:50. After bolus intravenous doze and in the further course of the anesthetic and surgery propofol was administered via BRAUN perfusor, in the amount of 0.1-0.3 mg/kg/min.

In the sevourane group of patients, opioid fentanyl was administered at a dose of 0.005 mg/kg, followed by a muscle relaxant vecuronium-bromide 10 minutes later at a dose of 0.1 mg/kg. During the administration of the opioid and muscle relaxant all sevourane group of patients received oxygen via anesthetic oxygen mask in the amount of 5 l/h. Immediately after administration of the muscle relaxant sevourane was administered from the appropriate dispenser on the anesthetic apparatus via anesthetic mask. The initial concentration of sevourane was 6 vol , and after each three respiratory cycles the value was reduced for one vol up to the value of 1 vol, which was maintained during the entire course of general endotracheal anesthesia. After achieving the state of sleep and muscle relaxation the patients were intubated with an appropriate size endotracheal tube. Continuous ventilation was achieved mechanically via anesthetic apparatus IPPV (Intermittent positive pressure ventilation). Tidal volume (breathing volume) and the respiration rate were adjusted to the age and weight of a child. The rate of inhaled gases during anesthesia was adjusted as follows: oxygen/ nitrogen oxide 50:50 with already stated sevourane value of 1 vol .

Immediately after the surgery, sevourane and nitrogen oxide were cut o in all patients from the sevourane group, and the oxygen ventilation was continued in the amount of 5 l/min. After the surgery and achievement of spontaneous ventilation, decurarization with neostigmine at a dose of 0.05 mg/kg and atropine at a dose of 0.02mg/ kg was performed in both groups of patients. Extubation was done after all criteria for safe extubation were met, specically, after meeting all criteria of good revision of neuromuscular blockade and criteria of the sleep-wake cycle.

Postoperative pain in both groups of patients was treated with analgesics (paracetamol, ibuprofen, metamizole, tramadol) as a suppository or intravenously according to the age and weight of the child. After waking up in the operating theatre patients from both groups were transferred to Pediatric Surgery of the University Clinical Center Sarajevo (UCCS) for further treatment.

3. RESULTS

In our study we obtained the following results:

Med Arh. 2015 Aug; 69(4): 218-221

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Quality and Safety of General Anesthesia with Propofol and Sevourane in Children Aged 1-14

Table 1 monitors movement of the serum glucose mean level in the preoperative and postoperative period in both groups of patients. In the preoperative period of the sevourane group of patients that level was 4.7 mmol/L, and 4.84 mmol/L in the propofol group of patients. In the postoperative period the serum glucose mean level in the sevourane group was 4.5 mmol/L, and 4.2 mmol/L in the propofol group. There was a statistically signicant dierence in the preoperative serum glucose mean level in the sevourane group in respect to the propofol group of patients (p=0.15)(Table 1).

Table 2 shows the creatinine mean level in preoperative and postoperative period in both groups of patients. In the preoperative period of the sevourane group of patients that level was 51.1 mmol/L, and 53.71 mmol/L in the propofol group of patients. In the postoperative period the creatinine mean level in the sevourane group of patients was 48.86 mmol/L, and 50.84 mmol/L in the propofol group of patients. Somewhat lower levels in the postoperative period in respect to the preoperative period (after 24h) were in their referential levels in both groups of patients and did not require any corrections. There was no statistically signicant dierence in creatinine mean levels between the propofol and sevourane group of patients either preopratively or postoperatively (Table 2).

Table 3 shows the urea mean level in preoperative and postoperative period in both groups of patients. In the preoperative period of the sevourane group of patients that level was 4.1 mmol/L, and 4.5 mmol/L in the propofol group of patients. The dierence was statistically signicant (p=0.016). In the postoperative period the urea

mean level in the sevourane group of patients was 4.34 mmol/L, and 44 mmol/L in the propofol group of patients. The dierence was not statistically signicant (p=0.9).

Table 4 shows the AST mean levels in the preoperative and postoperative period in both groups of patients. In the preoperative period of the sevourane group of patients that level was 28.2 U/L, and 26.00 U/L in the propofol group of patients. The dierence in the sevourane group was statistically signicantly higher than in the propofol group (28.2 U/L vs.26.0; p=0.03). In the postoperative period the AST mean level in the sevourane group was 25.40 U/L, and 24.56U/L in the propofol group. The dierence was not statistically signicant (p=0.268).

Table 5 monitors movement of the ALT mean level preopratively and postoperatively in both groups of patients. In the preoperative period of the sevourane group of patients that level was 21.26 U/L, and 24.16 U/L in the propofol group of patients. In the postoperative

Preoperatively

(n=80)

Postoperatively

(n=80)

Sevou-

rane Propofol

Sevou

rane Propofol Level 4.6-6.9 4.9-7.4 3.5-6.1 4.6-7.2 X 4.131 4.558 4.365 4.415S 1.073 1.151 0.934 1.030 SX 0.120 0.129 0.104 0.115

Median 4.2 4.4 4.4 4.3 Mann-Whitney

Test P = 0.016 P = 0.900

Table 3. Urea in the sevourane group vs. propofol group (n=80)

Preoperatively (n=80)

Postoperatively

(n=80)

Sevourane Propofol Sevourane Propofol Level 2.6-6.1 3.1-6.7 4.2-7.1 2.3-5.4 X 4.704 4.839 4.490 4.223S 0.557 0.627 0.870 0.494 SX 0.0623 0.0701 0.0972 0.0552

Median 4.7 4.8 4.4 4.2 Mann -

Whitney

Test

Preoperatively

(n=80)

P = 0.152 P = 0.021

Table 1. Blood sugar in patients treated with sevourane vs.

propofol (n=80)

Postoperatively (n=80)

Sevourane Propofol

Sevourane Propofol

Level 23-39 30-42 22-37 26-40 X 28.150 26.000 25.400 24.563 S 5.924 6.436 4.983 5.003 SX 0.662 0.720 0.557 0.559

Median 29 26 24 24 Mann-Whitney Test P = 0.031 P = 0.268

Table 4. AST levels in the sevourane group vs. propofol group

(n=80)

Preoperatively (n=80)

Preoperatively (n=80)

Postoperatively (n=80)

Sevourane Propofol

Sevourane Propofol

Level 42-72 52-74 45-69 46-70 X 51.063 53.712 48.862 50.837 S 9.650 11.333 10.481 10.356 SX 1.079 1.267 1.172 1.158

Median 51 54 50 50 Mann - Whitney Test P = 0.113 P = 0.325

Table 2. Creatinine level in the sevourane group vs. propofol

group (n=80)

Postoperatively (n=80)

Sevourane Propofol

Sevourane Propofol

Level 38-43 46-57 30-37 45-55 X 21.262 24.163 21.262 23.450 S 7.353 8.789 5.507 8.033 SX 0.822 0.983 0.616 0.898

Median 20 23 20 22 Mann-Whitney

Test P = 0.021 P = 0.058

Table 5. ALT levels in the sevourane group vs. propofol group

(n=80)

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Quality and Safety of General Anesthesia with Propofol and Sevourane in Children Aged 1-14

period the ALT mean level in the sevourane group was 21.26U/L, and 23.45 U/L in the propofol group. The stated levels show that there was no statistically signicant dierence between the groups.

4. DISCUSSION

The study included 160 respondents divided in two groups according to the anesthetic used (total intravenous anesthesia (TIVA) was used for a group with propofol and inhalation anesthesia was used for a group with sevourane), additionally divided according to the age and gender structure. Out of the total of 160 respondents there were 92 boys and 62 girls. In the sevourane group there were 46 boys and 34 girls and the propofol group included 52 boys and 28 girls. The age structure was taken as a parameter given that both propofol and sevourane were for a long time used for adults and gradually introduced for children, but their application to the youngest population, specically to children under 3 years started only a few years ago (9, 10).

Analysis of the preoperative and postoperative values of blood sugar did not show any statistically signicant differences between the respondent groups (Table 1). In the preoperative period of the sevourane group of patients that level was 4.7 mmol/L, and 4.84 mmol/L in the propofol group of patients. In the postoperative period the serum glucose mean level in the sevourane group was 4.5 mmol/L, and 4.2 mmol/L in the propofol group. Somewhat lower levels in the postoperative period in respect to the preoperative period (after 24h) were in their referential levels in both groups of patients and did not require any corrections (?). A study conducted by Mujagic Z et al. in 2007 monitored the serum glucose concentration in patients surgically treated in propofol/fentanyl total intravenous anesthesia (TIVA) vs. balanced isourane/fentanyl anesthesia. The blood sugar levels were measured in 5 periods: 30 minutes before the surgery (T0), during the surgery (T1), after the surgery and anesthesia (T2), and after 2 and 24 hours respectively (T3 and T4) in the postoperative period. The serum glucose concentrations measured in the stated periods were signicantly lower especially in T1, T2 and T3 than in the preoperative period (T0) in propofol/fentanyl total intravenous anesthesia then in patients treated with balanced isourane/fentanyl technique. The results of the study show that the metabolic response to surgical treatment and anesthesia was probably allayed, specically improved in patients treated in the propofol/fentanyl total intravenous anesthesia in respect to those treated in balanced isourane/fentanyl technique (11).

Comparison of the preoperative and postoperative urea and creatinine levels did not show any statistically significant dierences as well as the comparison of transaminases between the groups (Table 2, 3, 4, 5). A study conducted by Mazze R et al. in 2000, which included 3,436 patients, monitored preoperative and postoperative urea and creatinine levels in use of dierent hypnotics and anesthesia techniques. The TIVA technique propofol, inhalation technique sevourane, isourane, enurane. The obtained results imply stable values of the monitoring parameters both preopratively and postoperatively, which lead to a conclusion that the stated values may have sig-

nicant changes only in case those surgical treatments are performed on patients with already existing renal diseases (12), and not due to the hypnotics used.

Results of the blood transaminases analysis could not be

compared given that we could not nd any similar studies.

5. CONCLUSION

The values of laboratory parameters monitored during the study did not show statistically signicant dierences. Analysis of the examined laboratory parameters, in respect to others used anesthetic agents in everyday clinical practice, shows that propofol and sevourane provide full security and quality of general anesthesia in children age group 1-14 years, from ASA I group. Based on the obtained results and taking into account minimal technical preparations for TIVA and inhalation anesthesia, easy handling and control of the anesthetics, simplicity of keeping and storage as well as efficiency of sevourane and propofol give them priority above other anesthetics recently used in pediatric anesthesia.

CONFLICT OF INTEREST: NONE DECLARED.

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