RU2847017C1 - Method for xenon-saving maintenance of anaesthesia - Google Patents

Abstract

FIELD: medical science.

SUBSTANCE: present invention refers to medicine, namely to anaesthesiology. It may be used for combined inhalation anaesthesia. Method is implemented as follows: after induction of anaesthesia by inhalation of sevoflurane 8 vol.% in oxygen flow 8 l/min and intravenous administration of propofol 2 mg/kg maintenance of anaesthesia is carried out by intravenous administration of atropine at dose of 0.01 mg/kg and propofol – 2.5 mg/kg/h, with simultaneous disconnection of sevoflurane supply. That is combined with inhalation of a gas narcotic mixture oxygen : xenon in ratio 30% : 70%, respectively. Total flow makes 2.5 l/min for one or one and a half minutes until the xenon concentration in the breathing circuit is 45%. Further gas flow is reduced to 150-200 ml/min with ratio of oxygen : xenon 55-60% : 40-45%, respectively.

EFFECT: method enables reducing consumption of the inhalation anaesthetic xenon with preserving its properties.

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Description

The present invention relates to anesthesiology and intensive care and is intended for use at the pre-hospital and hospital stages of providing medical care, including during outpatient interventions.

Optimizing general anesthesia techniques is of great importance in modern anesthesiology research and practice. Reducing the concentration of anesthetics maintaining anesthesia at a given level through rational combination is the key to optimal clinical results and the pharmacoeconomic success of modern anesthesia techniques. These include combinations of inhalation agents, interactions between inhalation and non-inhalation anesthetics, and a combination of regional anesthesia with inhalation and non-inhalation agents (Trashkova M.Yu., Lazarev V.V., "Using the Effect of Mutual Potentiation of Drugs for Inhalation and Intravenous Anesthesia" // General Medicine. 2011. No. 1). Such combinations are particularly relevant when using expensive anesthetics, such as xenon. Much research and study has been devoted to xenon-sparing technologies and methods. For example, in children with congenital heart disease, the addition of 60% xenon to sevoflurane results in a 60% reduction in the mean expiratory sevoflurane concentration to achieve sufficient depth of anesthesia (Devroe S, Mceusen R, Gewillig M, Cools B, Poesen K, Sanders R, Rex S. Xenon as an adjuvant to sevoflurane anesthesia in children younger than 4 years of age undergoing interventional or diagnostic cardiac catheterization: A randomized controlled clinical trial. Paediatr Anaesth. 2017 Dec; 27 (12): 1210-1219. dor: 10.1111/pan.l3230).

The non-inhalation anesthetic propofol is particularly popular in anesthesiology practice. Its success in clinical settings is due to its rapid onset of action, short duration of effect, and minimal side effects (Mahmoud M., Mason K.P. Recent advances in intravenous anesthesia and anesthetics. F1000R.es. 2018 Apr 17; 7: F1000 Faculty Rev-470. doi: 10.12688/f1000research. 13357.1. PM ID: 29755731). A meta-analysis shows that in adults, xenon provides greater hemodynamic stability and faster recovery from anesthesia using inhalational anesthetics and propofol (Law L.S., Lo E.A., Gan T.J. Xenon Anesthesia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Anesth Analg. 2016 Mar; 122 (3): 678-697. doi: 10.1213/ANE.0000000000000914). The effect of xenon on systemic hemodynamics, cerebral blood flow, and intracranial pressure has been demonstrated in many ongoing studies (aw L.S., Lo E.A., Gan T.J. Xenon Anesthesia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Anesth Analg. 2016 Mar; 122 (3): 678-697. doi: 10.1213/ANE.00000000000000914). Stable intracranial pressure and cerebral blood flow, and neuroprotection make the inhalation anesthetic xenon promising for patients with compromised central nervous system. A proven clinical effect of a therapeutic dose of propofol is a decrease in cerebral blood flow (Ederberg S., Westerlind A., Houltz E., Svensson S.E., Elam M., Ricksten S.E. The effects of propofol on cerebral blood flow velocity and cerebral oxygen extraction during cardiopulmonary bypass. Anesth Analg. 1998 Jun; 86 (6): 1201-6. doi: 10.1097/00000539-199806000-00011), which in combination with xenon may be optimal for patients with increased intracranial pressure.

The feasibility of combining the above-mentioned anesthetics in low doses to improve intraoperative cerebral perfusion in neurosurgical patients was found in the work of Russian researchers (Rylova A.V., Gavrilov A.G., Lubnin A.Yu., Potapov A.A. Intracranial and cerebral perfusion pressure in neurosurgical patients during xenon anesthesia // Anesthesiology and resuscitation. 2014. No. 4).

Thus, the combination of the inhalation anesthetic xenon and the intravenous anesthetic propofol appears interesting and promising, reducing the concentration of both drugs without losing their positive properties.

The purpose of the invention: rational reduction of the concentration of xenon to 40-45% and propofol to 2.5 mg/kg/h in the protocol for performing combined inhalation anesthesia at the stage of maintaining anesthesia without loss of clinical and pharmacological effects.

The method is demonstrated by the following clinical examples.

Example 1

The parents of 3-year-old patient A. sought oral sanitation under combined inhalation anesthesia at the multidisciplinary clinic, OOO Dental Forte. A routine preoperative examination, instrumental tests, and laboratory tests revealed no abnormalities. Combined general anesthesia with xenon and propofol was chosen for the anesthesia.

The efficacy and safety of anesthesia were assessed based on systolic (BPs), diastolic (BPd), mean (BPsr) blood pressure data, heart rate (HR) using a Comen star 8000 s monitor (China), BIS index data [MGA-06 anesthesia depth assessment monitor (Russia)], and lung ventilation parameters: respiratory rate (RR) Paw (airway pressure, mmHg), MV (minute ventilation, l/min), Vte (expiratory volume), Vti (inspiratory volume), _FiO2 (oxygen concentration in the inhaled gas mixture), _EtCO2 ( _CO2 concentration at the end of exhalation), monitored by the built-in module of the anesthesia machine. Blood gas composition was assessed in capillary blood using an iStat analyzer (USA), the pressure in the cuff of the endotracheal tube was controlled by a device for monitoring pressure in the endotracheal tube. Portex tube (UK), intravenous infusion of propofol was carried out using an SN-50F6 syringe infusion pump (China).

Anesthesia was induced without premedication using sevoflurane (Sev) using the bolus technique: the breathing circuit of the Chirana VENAR Libera Screen (TS + AGAS) anesthesia and respiratory apparatus (ARA) was pre-filled with a mixture of O2 (8 l/min) and Sev (with an inspiratory concentration of 8 vol.%) by sequentially filling and emptying the breathing bag three times, after which the gas-anesthetic mixture was administered to the child through a face mask. By the 7th-10th breath, the child lost consciousness. Venous access was then established, during which the BIS index value was 60 U.S. Atropine at a dose of 0.01 mg/kg and propofol 2 mg/kg were administered intravenously to reduce salivation and muscle tone. Tracheal intubation was then performed with a BIS index of 40 units. The child was then transferred to mechanical ventilation in spontaneous breathing mode with pressure support ventilation (PSV).

Xenon (Xe) inhalation began the moment the dentist began working. The child's body was also saturated with xenon in the PSV mode. Ventilation parameters were set according to the child's individual needs and were aimed at reducing the work of breathing. The adequacy of the selected ventilation mode was assessed by patient-ventilator synchronization (flow graph, airway pressure), hemodynamic stability, acid-base balance indicators, and adequate _SpO2 . Compliance with the child's tidal volume during the respiratory cycle was also assessed. The total flow of the gas-anesthetic mixture was set at 2.5 liters per minute, of which _O2 accounted for 30% of the mixture and xenon for 70%, or approximately 1.75 liters. Within 1.5 minutes, the xenon concentration in the circuit reached 45%. Next, the flow rate was switched to 150-200 ml/min with an _O2 :Xe ratio of 55-60:45-40%. The sevoflurane concentration on the vaporizer was set to 0, maintaining the MAC in the circuit at 0.1. After tracheal intubation, propofol was continuously administered intravenously at a dose of 2.5 mg/kg. BIS index values remained at 45-55 units throughout the treatment period. The monitored parameters are presented in Table 1.

Propofol administration was stopped 10 minutes before the dentist completed their work. Xenon was turned off simultaneously with the dentist's completion of their work, and the _O2 flow was increased to 5 L/min. One minute and 30 seconds after the Xe anesthetic was turned off, its content in the gas-anesthetic mixture reached 10%, and tracheal extubation was successfully performed. Three minutes after the end of treatment, the child opened his eyes, and 15 minutes after the end of anesthesia, consciousness was assessed as having returned to baseline. No signs of postanesthesia agitation were noted. Anesthesia duration was 2 hours 10 minutes. The volume of xenon consumed was 4.9 liters.

Example 2

The parents of 4-year-old patient F. visited the multidisciplinary clinic "OOO Dental Forte" for oral sanitation under combined inhalation anesthesia. A routine preoperative examination, instrumental tests, and laboratory tests revealed no abnormalities. Combined general anesthesia with xenon and propofol was chosen for the anesthesia.

The efficacy and safety of anesthesia were assessed based on systolic (BPs), diastolic (BPd), mean (BPsr) blood pressure data, heart rate (HR) using a Comen star 8000c monitor (China), BIS index data [MGA-06 anesthesia depth assessment monitor (Russia)], and lung ventilation parameters: respiratory rate (RR) Paw (airway pressure, mmHg), MV (minute ventilation, l/min), Vte (expiratory volume), Vti (inspiratory volume), _FiO2 (oxygen concentration in the inhaled gas mixture), _EtCO2 ( _CO2 concentration at the end of exhalation), monitored by the built-in module of the anesthesia machine. Blood gas composition was assessed in capillary blood using an iStat analyzer (USA), the pressure in the cuff of the endotracheal tube was controlled by a device for monitoring pressure in the endotracheal tube. Portex tube (UK), intravenous infusion of propofol was carried out using an SN-50F6 syringe infusion pump (China).

Anesthesia was induced without premedication using sevoflurane (Sev) using the bolus technique: the breathing circuit of the Chirana VENAR Libera Screen (TS + AGAS) anesthesia and respiratory apparatus (ARA) was pre-filled with a mixture of _O2 (8 l/min) and Sev (with an inspiratory concentration of 8 vol.%) by sequentially filling and emptying the breathing bag three times, after which the gas-anesthetic mixture was administered to the child through a face mask. By the 7th-10th breath, the child lost consciousness. Venous access was then established, during which the BIS index value was 60 U.S. Atropine at a dose of 0.01 mg/kg and propofol 2 mg/kg were administered intravenously to reduce salivation and muscle tone. Tracheal intubation was then performed with a BIS index of 40 units. The child was then transferred to mechanical ventilation in spontaneous breathing mode with pressure support ventilation (PSV).

Xenon (Xe) inhalation began the moment the dentist began working. The child's body was also saturated with xenon in the PSV mode. Ventilation parameters were adjusted to the child's individual needs and aimed at reducing the work of breathing. The adequacy of the selected ventilation mode was assessed by patient-ventilator synchronization (flow graph, airway pressure), hemodynamic stability, acid-base balance indicators, and adequate _SpO2 . The correspondence of the child's tidal volume to its calculated value during the respiratory cycle was also assessed. The total flow of the gas-anesthetic mixture was set at 2.5 liters per minute, of which _O2 accounted for 30% of the mixture and xenon for 70%, or approximately 1.75 liters. Within 1.5 minutes, the xenon concentration in the circuit reached 45%. Next, the flow rate was switched to 150-200 ml/min with an _O2 :Xe ratio of 55-60:45-40%. The sevoflurane concentration on the vaporizer was set to 0, maintaining the MAC in the circuit at 0.1. After tracheal intubation, propofol was continuously administered intravenously at a dose of 2.5 mg/kg. BIS index values remained at 45-55 units throughout the treatment period. Monitored parameters are presented in Table 2.

Propofol administration was stopped 10 minutes before the dentist completed their work. Xe administration was stopped simultaneously with the dentist's completion of their work, and the _O2 flow was increased to 5 L/min. One minute after the anesthetic was switched off, its content in the gas-anesthetic mixture reached 10%, and tracheal extubation was successfully performed. Five minutes after the end of treatment, the child opened his eyes, and 15 minutes after the end of anesthesia, consciousness was assessed as restored to baseline. No signs of postanesthetic agitation were noted. Anesthesia duration was 3 hours. The volume of xenon consumed was 6.7 liters.

Example 3

The parents of 5-year-old patient A. sought oral sanitation under combined inhalation anesthesia at the multidisciplinary clinic, OOO Dental Forte. A routine preoperative examination, instrumental tests, and laboratory tests revealed no abnormalities. Combined general anesthesia with xenon and propofol was chosen for the anesthesia.

The efficacy and safety of anesthesia were assessed based on systolic (BPs), diastolic (BPd), mean (BPsr) blood pressure data, heart rate (HR) using a Comen star 8000 s monitor (China), BIS index data [MGA-06 anesthesia depth assessment monitor (Russia)], and lung ventilation parameters: respiratory rate (RR) Paw (airway pressure, mmHg), MV (minute ventilation, l/min), Vte (expiratory volume), Vti (inspiratory volume), _FiO2 (oxygen concentration in the inhaled gas mixture), _EtCO2 ( _CO2 concentration at the end of exhalation), monitored by the built-in module of the anesthesia machine. Blood gas composition was assessed in capillary blood using an iStat analyzer (USA), the pressure in the cuff of the endotracheal tube was controlled by a device for monitoring pressure in the endotracheal tube. Portex tube (UK), intravenous infusion of propofol was carried out using an SN-50F6 syringe infusion pump (China).

Anesthesia was induced without premedication using sevoflurane (Sev) using the bolus technique: the breathing circuit of the Chirana VENAR Libera Screen (TS + AGAS) anesthesia and respiratory apparatus (ARA) was pre-filled with a mixture of _O2 (8 l/min) and Sev (with an inspiratory concentration of 8 vol.%) by sequentially filling and emptying the breathing bag three times, after which the gas-anesthetic mixture was administered to the child through a face mask. By the 7th-10th breath, the child lost consciousness. Venous access was then established, during which the BIS index value was 60 U. To reduce salivation and muscle tone, atropine at a dose of 0.01 mg/kg and propofol 2 mg/kg were administered intravenously. Tracheal intubation was then performed with a BIS index of 40 units. The child was then transferred to mechanical ventilation in spontaneous breathing mode with pressure support ventilation (PSV).

Xenon (Xe) inhalation began the moment the dentist began working. The child's body was also saturated with xenon in the PSV mode. Ventilation parameters were adjusted to the child's individual needs and aimed at reducing the work of breathing. The adequacy of the selected ventilation mode was assessed by patient-ventilator synchronization (flow graph, airway pressure), hemodynamic stability, acid-base balance indicators, and adequate _SpO2 . The correspondence of the child's tidal volume to its calculated value during the respiratory cycle was also assessed. The total flow of the gas-anesthetic mixture was set at 2.5 liters per minute, of which _O2 accounted for 30% of the mixture and xenon for 70%, or approximately 1.75 liters. Within 1.5 minutes, the xenon concentration in the circuit reached 45%. Next, the flow rate was switched to 150-200 ml/min with an _O2 :Xe ratio of 55-60:45-40%. The sevoflurane concentration on the vaporizer was set to 0, maintaining the MAC in the circuit at 0.1. After tracheal intubation, propofol was continuously administered intravenously at a dose of 2.5 mg/kg. BIS index values remained at 45-55 units throughout the treatment period. The monitored parameters are presented in Table 3.

Propofol administration was completed 10 minutes after the dentist completed their work. Xe administration ceased simultaneously with the dentist's completion, and the _O2 flow was increased to 5 L/min. Two minutes and 45 seconds after the anesthetic was switched off, its content in the gas-anesthetic mixture reached 10%, and tracheal extubation was successfully performed. The child opened his eyes 4 minutes and 30 seconds after the end of treatment, and consciousness was assessed as restored to baseline 20 minutes after the end of anesthesia. No signs of postanesthetic agitation were noted. Anesthesia duration was 2 hours and 30 minutes. The volume of xenon consumed was 6 liters.

Thus, the presented method reduces the consumption of the expensive inhalational anesthetic xenon by using continuous intravenous propofol administration, while maintaining the beneficial properties of xenon. No signs of postanesthesia agitation were observed. Anesthesia duration was 2 hours 30 minutes. The volume of xenon consumed was 6 liters.

Thus, the presented method allows for a reduction in the consumption of the expensive inhalational anesthetic xenon through continuous intravenous propofol administration, while maintaining the beneficial properties of xenon. By assessing hemodynamic, ventilation, acid-base balance, and BIS monitoring parameters, we conclude that the monitored parameters are stable and adequate.

To date, 13 anesthesia procedures of varying complexity and duration have been performed using this technique in the Dental Forte LLC clinic network in Naberezhnye Chelny.

This method was developed by us for the first time and is completely ready for use in medical institutions of all levels providing medical care in inpatient and outpatient settings using anesthesia.

Claims (1)

A method for xenon-sparing maintenance of anesthesia, characterized in that after induction of anesthesia by inhalation of 8 vol.% sevoflurane in an oxygen flow of 8 l/min and intravenous administration of atropine at a dose of 0.01 mg/kg propofol 2 mg/kg, anesthesia is maintained by intravenous administration of propofol at a dose of 2.5 mg/kg/h with simultaneous shutdown of the sevoflurane supply and the beginning of inhalation of a gas-anesthetic mixture of oxygen:xenon in a ratio of 30%:70%, respectively, with a total flow of 2.5 l/min for one to one and a half minutes until the xenon concentration in the breathing circuit reaches 45%, followed by a decrease in the gas flow to 150-200 ml/min at a ratio of _O2 :Xe = 55-60:45-40%.