RU2635532C1 - Method for prevention of agitation syndrome in children with oncological pathology - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: methodincludes single intranasal injection of dexmedetomidine at a dose of 2 mcg/kg prior to anesthesia with sevoflurane on a semi-open contour with maintained spontaneous breathing. Application of the invention makes it possible to achieve pre-anesthesia sedation level R3-R5 on the Ramsey scale without respiratory depression, development of analgesic effect.

EFFECT: decrease in MAC of sevoflurane, prolongation of postnarvic sleep, a decrease in intracranial pressure, level of cerebral blood flow, and brain oxygen consumption.

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Description

A method for the prevention of agitation syndrome in children with oncological pathology arising from high-flow inhalation mask anesthesia with sevoflurane in a half-open circuit with preserved spontaneous breathing.

The invention relates to medicine, namely to children's anesthesiology, and can be used to prevent agitation that occurs after anesthesia with sevoflurane, as well as to reduce anxiety and anxiety during transportation of the child to the operating room and weaning him from his parents.

Therapy of oncological diseases in children involves a series of painful manipulations under anesthesia. For this purpose, high-flow inhalation monoanesthesia with sevoflurane is carried out with preserved spontaneous respiration without prior sedation. Premedication with currently available benzodiazepine drugs (Relium, Sibazon) in the absence of venous access provides an exclusively intramuscular route of administration, which in itself causes a lot of negative emotions in babies and does not lead to the development of a proper sedative effect.

Sevoflurane inhalation anesthesia is the gold standard in pediatric anesthesiology. This anesthetic does not irritate the upper respiratory tract, has a cardioprotective effect, is easily controlled, has a dose-dependent effect, low toxicity, provides rapid induction and quick wake up after anesthesia (see Gregory J.A. Anesthesia in pediatrics. M .: Medicine; 2003. - c 1178), (see Mikhelson V.A., Sidorov V.A., Stepanenko S.N. Anesthesia and intensive care in pediatrics. // Short practical guide. M. - 2007. - p. 125).

Along with this, sevoflurane has some side effects. Of greatest interest, from the point of view of assessing the negative effect of sevoflurane on the child’s body, the so-called agitation or syndrome of post-narcotic excitation (STD) is of great interest (see Lazarev V.V., Tsypin L.E. Syndrome of post-narcotic excitation during inhalation anesthesia with sevoflurane in children // Journal Anesthesiology and Intensive Care - 2010. - No. 1. - S. 62-66). SPEC is manifested in the form of severe anxiety, motor excitement, pronounced negativity, loss of focus of actions, lack of contact. The reaction of parents observing agitation in children during the period of awakening is often mixed: from fear for the child to aggression against medical staff. According to various sources, the incidence of STDV varies from 6 to 80% (see Lazarev V.V., Tsypin L.E. Syndrome of post-narcotic excitation during inhalation anesthesia with sevoflurane in children // Journal of Anesthesiology and Intensive Care - 2010. - No. 1. - P. 62-66.), (See Sabinina TS, Gubaidullin PP, Pasechnik IN, Bagaev VG, Mikheev MV X scientific-practical conference "Safety of the patient in anesthesiology and intensive care" M. - 2012), (see Cravero JP, Beach M., Dodgt S.P. et al. J. Clin. Anaesth. - 2000. - Vol. 12. - No. 5. - P. 397-401). Our studies indicate that in children with cancer, excitation after anesthesia with sevoflurane occurs in 65% of cases.

To date, there is no final opinion regarding the etiology and pathogenesis of the agitation syndrome. Among the causes, rapid recovery of consciousness against a background of insufficient analgesia is distinguished (see Tsypin L.E., Lazarev V.V., Korsunsky A.A., Prokopyev G.G., Schukin V.V., Vaganov N.N., Bolotov AA, Kochkin BC, Linkova TV “Inhaled anesthesia with sevoran (sevoflurane) in children. - Methodological manual. - M .: RSMU, 2008. - p. 19), restless behavior of the child before anesthesia, lack of premedication with benzodiazepines (see Ignatenko D.Yu., Utkin S.I. Prevention of excitation syndrome during anesthesia with sevoflurane in pediatric ophthalmic surgery // Fedorov Readings. 2009). One of the possible reasons may be an increase in intracranial pressure (ICP) against the background of inhalation of sevoflurane. As you know, sevoflurane causes a dose-dependent increase in ICP and an increase in cerebral blood flow (see L.E. Tsypin, V.V. Lazarev, A.A. Korsunsky, G.G. Prokopyev, V.V. Schukin, N.N. Vaganov , AA Bologov, BC Kochkin, TV Linkova, Inhalation anesthesia with Sevoran (Sevoflurane) in children. - Methodical manual. - M .: RSMU, 2008. - p. 17). In the study, Spaner R.Ya. and Bayalieva A.Zh. The effect of an inhaled anesthetic (sevoflurane) and propofol on intracranial pressure during neurosurgical interventions (see Russian Neurosurgery. - 2009. - No. 1 - P. 94), it was proved that during anesthesia with sevoflurane an increase in ICP values by 12-15% was noted. Sevoflurane, being a cerebral vasodilator, increases cerebral blood flow (MK) and disrupts its autoregulation. With an increase in MK, intracranial blood volume increases and, as a consequence, ICP increases (see Zeitlin AM Use of propofol in neuroanesthesiology. Text. / AM Zeitlin, A.Yu. Lubnin // Russian Journal of Anesthesiology and Intensive Care. 1999, No. 1. - P. 21-22).

A significant number of studies are devoted to measures for the prevention and relief of the agitation syndrome during anesthesia with sevoflurane. So, for example, for this purpose it is recommended to use opioid analgesics, ketamine, nitrous oxide, clonidine, benzodiazepines, propofol and dexmedetomidine (see Lazarev V.V., Tsypin L.E. Post-narcotic irritation syndrome during inhalation anesthesia with sevoflurane in children // Zhurn Anesthesiology and Intensive Care - 2010. - No. 1. - S. 62-66). For a number of reasons, many of these drugs cannot be used in pediatric oncology during short-term mask anesthesia with sevoflurane with preserved spontaneous breathing, because they cause respiratory depression (opioid analgesics), increase intracranial pressure, and realize their effect by inhibiting the function of neurons in the associative zone of the cerebral cortex and thalamus (ketamine), significantly lower blood pressure (clonidine), can cause hypoxemia against the background of concomitant anemia (nitrous oxide).

In order to prevent ADHD, it may be promising to use a selective agonist of a2-adrenergic receptors - dexmedetomidine (dexdor) in the form of intranasal premedication.

The main advantages of the intranasal use of drugs (PM) are:

1) The presence of the central action of drugs due to the fact that the shell of the olfactory nerves are devoid of the blood-brain barrier and drugs from the nasal cavity can immediately enter the brain.

2) High bioavailability.

3) The absence of the effect of the first passage through the liver and the associated adverse reactions.

4) Convenience and ease of use, which leads to improved patient compliance.

5) The rapidity of the development of the systemic effect (see Gurevich KG Development of intranasal drug delivery systems // Qualitative Clinical Practice. - 2002 - No. 1).

Dexmedetomidine has a wide range of pharmacological properties. It has a sedative and hypnotic effect, which is due to a decrease in the activity of noradrenergic neurons of the blue spot in the brain stem. In addition, it has a dose-dependent antinociceptive effect, which in turn makes it possible to reduce the doses of anesthetics and analgesics (see Dexdor (Dexmedetomidine): monographs on the drug. Orion Pharm; 2015).

The drug has practically no ability to depress respiration, since the sedative mechanism of dexmedetomidine is associated with the adrenergic pathway of the cerebral cortex activation (see Ebert T., Maze M. Dexmedetomidine: another arrow for the clinician's quiver. Anesthesiology 2004; 101: 568-570.22) , Dexmedetomidine has neuroprotective properties, and also helps prevent delirium and tremors (see Neema PK Dexmedetomidine in pediatric cardiac anesthesia. Ann Card Anaesth 2012; 15: 3: 177-179. DOI: 10.4103 / 0971-9784.97972), (see Tobias JD, Gupta P., Naguib A., Yates AR Dexmedetomidine: applications for the pediatric patient with congenital htart disease. Pediatr Cardiol 2011; 32: 8: 1075-1087.doi: 10.10 07 / s00246-011-0092-8). The administration of dexmedetomidine leads to a decrease in ICP and an increase in cerebral perfusion pressure (see Aryan N.E., Box KW, Ibra him D. et al. Safety and effecacy of dexmedetomidine in neurosurgical patients. Brain Inj. 2006; 20: 791-798 ), (see Zornow MH, Scheller MS, Sheehan PB et al. Intracranial pressure effects of dexmedetomidine in rabbits. Anesth. Analg. 1992; 75: 232-237). There is also a decrease in cerebral blood flow and a slight decrease in brain oxygen consumption (see Farag E., Argalious M., Sesler DI, et al. Use of alphas-agonists in neuroanesthesia: An overview. Ochsner J. 2011; 11 (1) : 57-69.7).

The prototype of the invention is a method for preventing post-narcotic anesthesia during anesthesia with sevoflurane (Ibacache M.E., Muzon HR, Brandes V. et al. Single-dose dexmedetomidine reduces agitation after sevoflurane anesthesia in children. Anest. Analg. 2004; 98: 1: 60- 63), consisting in a single intravenous administration of dexmedetomidine at a dose of 0.3 μg / kg at 10 minutes from the start of induction in anesthesia.

However, this method has some disadvantages, namely:

1. This method involves the on / in the introduction of dexmedetomidine at 10 minutes from the start of induction in anesthesia. The duration of anesthesia when performing painful manipulations in pediatric oncology, as a rule, does not exceed 30 minutes. The half-life of dexmedetomidine when administered intravenously is approximately 2 hours. Thus, an unreasonably long post-narcotic sedation develops, which leads to late activation of the child and an extension of the “hungry” pause.

2. The method is applicable only with venous access.

3. This method does not prevent the child's arousal before anesthesia, thus it does not exclude one of the risk factors for the development of agitation syndrome.

In connection with the foregoing, there is a need for the search and development of new approaches to the prevention of post-anesthetic agitation and the prevention of arousal before anesthesia.

The technical result of the invention consists in the development of pre-narcotic sedation corresponding to the R3 - R5 level on the Ramsey scale, without respiratory depression, in the development of an analgesic effect, which allows to reduce the MAC of sevoflurane, to prolong the time of post-narcotic sleep, to reduce intracranial pressure, the level of cerebral blood flow and consumption brain oxygen.

The specified technical result is achieved due to the fact that before anesthesia, a single intranasal administration of the drug dexmedetomidine at a dose of 2 μg / kg is carried out.

The proposed method of anesthesia is as follows. 30 minutes before the start of anesthesia, we intranasally administer dexmedetomidine at the rate of 2 μg / kg using a syringe labeled U-100. After the development of a sedative effect, we take the child to the operating room, where we perform high-flow inhalation mask anesthesia with sevoflurane along a half-open circuit with spontaneous breathing preserved.

Therefore, the prevention of excitement before anesthesia, a decrease in intracranial pressure against the background of an elongation of the phase of post-narcotic drug sleep, a decrease in the intensity of pain impulse with a decrease in the MAF of sevoflurane, ensures a quiet exit from anesthesia and the absence of post-anesthetic agitation.

The authors in the patent and scientific literature did not find information about the fame of the proposed method of anesthesia when performing painful manipulations for children with cancer. Thus, the claimed invention meets the criterion of "novelty."

According to our research, anxiety, fear, and severe anxiety at the stage of transporting a child to the operating room and weaning him from his parents are observed in 100% of young children. The introduction of dexmedetomidine intranasally 30 minutes before the start of anesthesia leads to the rapid development of a sedative effect and prevents agitation. Dexmedetomidine levels the increased intracranial pressure and cerebral blood flow increased due to inhalation of sevoflurane, including due to a decrease in the target concentration of sevoflurane. The lengthening of the post-narcotic drug sleep phase in combination with the analgesic-saving effect of dexmedetomidine helps to reduce the intensity of pain impulse. Thus, the claimed invention meets the criterion of "inventive step".

To assess the effectiveness of the proposed method for the prevention of post-anesthesia arousal, we used the determination of systolic, diastolic, mean blood pressure, heart rate, SpO _{2 with a} PHILIPS M3046A monitor, MAK sevoflurane, et CO ₂ , Fi O _{2 with a} Datex-Ohmeda Cardiocap / 5 monitor, determination of the index of bispectral analysis of the electroencephalogram Aspekt A-1000 monitor. A clinical assessment of sedation was performed using the Ramsey scale.

We give examples of clinical use of the proposed method.

Example 1

Patient T., 3 years old, weight 12.5 kg.

Diagnosis: nephroblastoma on the right, the state after nephrectomy on the right.

Manipulation: catheterization of the subclavian vein.

Anamnesis: chin tremor, head tilting back, difficulty falling asleep, meteosensitivity. Severe arousal during weaning from parents and on awakening after inhalation anesthesia with sevoflurane.

30 minutes before the start of anesthesia: blood pressure 95/50 mm Hg, heart rate - 116 per min, vegetative Kerdo index - 56.9. Intranasally introduced dexmedetomidine in an amount of 25 μg. Little concern after administration of the drug persisted for 5 minutes, after which the child fell asleep. 30 minutes after the introduction of dexmedetomidine, the child was taken to the operating room. Upon admission, the baby is sleeping. Sedation R5.

Induction: inhalation of sevoflurane 8 vol. % in an oxygen stream of 10 l / min for 2 minutes. Further, inhalation of sevoflurane 4 vol. % in an oxygen stream of 4 l / min. within 2 minutes After 4 minutes from the start of anesthesia, the IIIA stage of anesthesia was reached. Potentiation was carried out by inhalation of sevoflurane 3 vol. % in an oxygen stream of 4 l / min. After 8 minutes from the start of anesthesia, subclavian vein catheterization, blood sampling for examination, and catheter fixation were performed. At 18 minutes from the start of anesthesia, the flow of sevoflurane was stopped, inhalation of 100% oxygen through the face mask was continued for 6 minutes, until the concentration of anesthetic on the exhale became equal to zero, after which the flow of oxygen was stopped and the child was transferred to breathing by atmospheric air. In a state of drug sedation corresponding to the R 3 level on the Ramsey scale, the child was transferred to the ward of the profile department under the supervision of a doctor. The position of the child during transportation - lying on its side, without a pillow. The duration of post-anesthetic sleep was 60 minutes, after which the child calmly woke up and ate.

The hemodynamic data, SpO ₂ , BIS indicators, sedation levels are presented in table No. 1.

Example 2

Patient E., 2 years 11 months, weight 14 kg. Diagnosis: mediastinal tumor.

Manipulations: transthoracic puncture biopsy of the mediastinal tumor, iliac puncture, bone marrow sampling for examination.

History: entanglement of the umbilical cord around the neck at birth, atrophy of the facial nerve, restless short-term sleep, restlessness.

30 minutes before the start of anesthesia: blood pressure 80/47 mm Hg, heart rate - 91 per minute, Kerdo vegetative index - 48.4. Dexmedetomidine was intranasally administered in an amount of 28 mcg. 10 minutes after the drug was administered, the child became lethargic, drowsy. 30 minutes after the introduction of dexmedetomidine, the child was taken to the operating room. Upon admission, the child is conscious, drowsy. Separated from her parents calmly. Sedation Level R1.

Induction: inhalation of sevoflurane 8 rpm in an oxygen stream of 10 l / min for 2 minutes. Further, inhalation of sevoflurane 4 vol. % in an oxygen stream of 4 l / min. within 2 minutes After 6 minutes from the start of anesthesia, the IIIA stage of anesthesia was reached. Potentiation was carried out by inhalation of sevoflurane 3 vol. % in an oxygen stream of 4 l / min. Over the next 22 minutes, the following were performed: the child turned on his left side, ultrasound navigation, puncture biopsy of the tumor. After 30 minutes from the start of anesthesia, the iliac crest was punctured to the right, and a bone marrow was taken for examination. At the 34th minute from the beginning of anesthesia, after the completion of the painful manipulations, the supply of sevoflurane was stopped, the inhalation of 100% oxygen through the face mask was continued for 6 minutes, until the concentration of the anesthetic on the exhale became zero, after which the supply of oxygen was stopped and the child was transferred to breathing by atmospheric by air. After 42 minutes from the onset of anesthesia, in a state of drug sedation corresponding to the R 3 level on the Ramsey scale, the child was transferred to the ward of the profile department under the supervision of a doctor. The position of the child during transportation - lying on its side, without a pillow. The duration of post-anesthetic sleep was 45 minutes, after which the child calmly woke up and ate.

The data of hemodynamics, SpO ₂ , indicators of BIS, sedation level are presented in table 2.

The proposed method for the prevention of post-anesthesia syndrome syndrome was used in 30 patients aged 1 to 4 years when performing painful manipulations.

The proposed method for the prevention of CVD is easily reproducible in a hospital setting. Thus, the claimed invention meets the criterion of "industrial applicability".

Claims (1)

A method for the prevention of agitation syndrome in children with oncological pathology arising from high-flow inhalation mask anesthesia with sevoflurane in a half-open circuit with preserved spontaneous breathing, including a single intranasal administration of the drug dexmedetomidine at a dose of 2 μg / kg before anesthesia.