RU2713838C1 - Method for anesthesia providing selective delivery of chemopreparation to the retina in the treatment of intraocular retinoblastoma in children - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to anesthesiology-resuscitation, ophthalmology, oncology and endovascular surgery, and can be used for anesthesia in the selective delivery of the chemopreparation to the retina in the treatment of intraocular retinoblastoma in children. That is ensured by induction and maintenance of anesthesia with sevoflurane, muscular relaxation with rocuronium, heparin prophylaxis following femoral artery puncture and catheterisation, dexamethasone and epinephrine. It involves pneumoprotective artificial pulmonary ventilation with preventive step-by-step increase of inhalation pressure in the upper respiratory tract 3 minutes before catheterization of a.ophthalmica. After catheterisation of a.ophtalmica at the moment of the first respiratory motion with decreasing compliance of lungs, 0.5 mcg/kg of epinephrine is injected with a bolus, pressure is increased by inhalation of Pinsp so that the respiratory volume is not less than 50 % of the initial one, the respiratory rate is increased by 1.5 times. If the level of the average blood pressure drops below 60 mm Hg after bronchospasm resolution, hemodynamics is supported by an adrenaline solution infusion in dose of 0.15 mcg/kg/min. If the manifestations of trigemino-pulmonary reflex are weak and moderate before waking up, 10 % calcium gluconate 1.0 ml and analgin in amount of 0.1 ml are introduced intravenously. Retrobulbar blockade is performed in the children with the expressed degree of reaction in the repeated procedures after the anesthesia induction.

EFFECT: method provides higher safety of anesthesia ensured by reducing the risk of cardiorespiratory disorders, prevention of trigemino-pulmonary reflex and reduction of degree of its manifestation.

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Description

The invention relates to medicine, namely to anesthesiology-resuscitation, oncology and endovascular surgery, and can be used to improve patient safety during anesthesiology during the selective delivery of a chemotherapy drug to the retina in the treatment of intraocular retinoblastoma in children from birth.

Retinoblastoma (RB) is the most common malignant disease in newborns; it occurs in a population of 1 in 20,000 newborns. The annual incidence is 10-14 people under the age of 5 years. RB accounts for 11% of cancer developing in the first year of life. Significant successes in treatment have been achieved largely due to the development of selective intra-arterial chemotherapy (CIAHT) techniques. One of the problems that arise during CIAHT is the prevention and relief of cardio-respiratory disorders (bronchospasm, alveolospasm, hypotension, bradycardia and with delayed treatment of asystole) that occur when contrast or any other fluid is introduced after catheterization a. Ophtalmica during repeated procedures [Kato MA, Green N, O'Connell K, Till SD, Kramer DJ, Al-Khelaifi M, Han JH, Pryor KO, Gobin YP, Proekt A: A retrospective analysis of severe intraoperative respiratory compliance changes during ophthalmic arterial chemosurgery for retinoblastoma. Paediatr Anaesth 2015; 25: 595-602], [Phillips TJ, McGuirk SP, Chahal HK, Kingston J, Robertson F, Brew S, Roebuck D, Hungerford JL, Herod J: Autonomic cardio-respiratory reflex reactions and superselective ophthalmic arterial chemotherapy for retinoblastoma. Paediatr Anaesth 2013; 23: 940-5. Kato MA, Green N, O'Connell K, Till SD, Kramer DJ, Al-Khelaifi M, Han JH, Pryor KO, Gobin YP, Proekt A: A retrospective analysis of severe intraoperative respiratory compliance changes during ophthalmic arterial chemosurgery for retinoblastoma. Paediatr Anaesth 2015; 25: 595-602.].

A known method of conducting anesthesia during the selective delivery of a chemotherapeutic drug to the retina in the treatment of intraocular retinoblastoma in children, which includes: the induction and maintenance of anesthesia with sevoflurane with a minimum alveolar concentration of 1, muscle relaxation with rocuronium 0.6 mg / kg after induction, the introduction of oxymetazoline 0.05% spray into the ipsilateral nasal passage, 100% oxygen concentration after skin puncture for intra-arterial catheter, the introduction of dexamethasone 0.5 mg / kg during repeated procedures, the beginning of hep infusion arina 80 U / kg after catheterization of the femoral artery, administration of epinephrine 0.5-1 μg / kg with increased pulmonary resistance. SIAHT [Jeacques H.S., Jung N.N., Pierre Y .. Anesthesia for ophthalmic artery chemosurgery. Anesthesiology 2017; No. 1; 126-165-72] This method is adopted as a prototype.

This method is recognized as not sufficiently effective [Nghe MS, Godier A, Shaffii A, et al. Prospective analysis of serious cardiorespiratory events in children during ophthalmic artery chemotherapy for retinoblastoma under a deep standardized anesthesia. Pediatric Anesthesia, 2018; 28: 120-6], since it has been revealed according to recent studies that the depth of general anesthesia and systemic analgesia does not affect the development of cardiorespiratory disorders.

The main disadvantage of the prototype is the inability to prevent and reduce severe reactions, especially in infants.

The objective of the invention is the creation of a new effective method for stopping, preventing and reducing the severity of cardiorespiratory disorders during intraarterial delivery of a chemotherapy drug to the retina in children with intraocular retinoblastoma, which will increase the safety of anesthesia in children.

Technical result

The inventive method allows to reduce the risk of cardiorespiratory disorders in the selective delivery of a chemotherapeutic drug to the retina of the eye, makes it possible to treat children with a pronounced degree of reaction, including infants up to 6 months, as well as to prevent the trigemino-pulmonary reflex and reduce its severity.

The invention is illustrated by figures 1 and 2.

The problem is solved in that the method includes the induction and maintenance of anesthesia with sevoflurane, muscle relaxation with rocuronium, heparin prophylaxis after puncture and catheterization of femoral autreria, the administration of dexamethasone and epinephrine, and differs in that they carry out pneumoprotective artificial ventilation of the lungs with a preventive step-by-step increase in respiratory pressure in the upper respiratory tract 2-3 min before catheterization of a.ophthalmica. After catheterization of a.ophtalmica: at the time of the first respiratory movement with a decrease in lung compliance, 0.3-0.5 μg / kg of adrenaline is administered as a bolus, Pinsp inspiration pressure is increased so that the tidal volume is not less than 50% of the initial one, increase the frequency respiration 1.5-2 times; with a decrease in the average blood pressure below 60 mm RT. Art. after resolving bronchospasm, hemodynamics are supported by infusion of an adrenaline solution, adhering to the target readings of ADsr 60-65 mm RT. Art. In cases of mild to moderate cardiorespiratory disorders, calcium preparations, such as calcium gluconate and NSAIDs, are administered before waking up for postoperative analgesia, such as analgin or perphalgan.

In children with a pronounced degree of reaction during repeated procedures, retrobulbar blockade is performed, which allows treatment of children, including infants up to 6 months, as well as the prevention of trigemino-pulmonary reflex and reduce its severity.

The inventive method is as follows.

1) Before the induction of anesthesia, a pre-installed central venous catheter is checked (installed a day before the procedure). Start: induction by an inhaled anesthetic Sevoflurane up to 8 vol%, O ₂ 6-8 l / min; establish monitoring: ECG (ECG leads should not be in the projection of the head / neck), saturation of venous blood (SpO ₂ ), blood pressure (BP); capnography, body temperature.

Before intubation, the following drugs are administered intravenously: dexamethasone at a dose of 0.15 mg / kg (but not more than 4 mg); atropine at a dose of 0.01 mg / kg in order to prevent bradycardia and to reduce the secretion of glands of the mucous membrane of the upper respiratory tract; Ondansetron in an age-related dosage for the prevention of postoperative nausea and vomiting.

Prepare the endotracheal tube (ETT, selected by weight / age), check the ETT cuff for leaks;

- muscle relaxation before laryngoscopy and intubation is achieved by intravenous administration of rocuronium at a dose of 0.6 mg / kg;

- all patients before intubation are administered opioid fentanyl at a dose of 2 μg / kg;

- direct sequential laryngoscopy, tracheal intubation.

2) Artificial ventilation of the lungs (mechanical ventilation) is carried out in Pressure Control mode, tidal volume (DO) at the rate of 7-8 ml / kg Considering the fact that hypercapnia is an independent risk factor for trigemino-pulmonary reflex in SIAHT, it is necessary to adhere to the strategy of moderate hyperventilation with EtCO ₂ 32-35 mm Hg. Art. Sedation is maintained by sevoflurane with a minimum alveolar concentration of 1 MAA. An adrenaline solution is prepared: adrenaline 0.1% 0.5 ml + NaCl solution 0.9% to 40.0 ml, the line is connected. The line with adrenaline should be washed, it is advisable to maintain it with trace infusion at a rate of 0.01-0.02 μg / kg / min (hemodynamically - not significant).

3) After puncture and catheterization by the surgeon of the femoral artery, heparin prophylaxis is started, which is carried out as follows: a heparin solution at a rate of 60 PIECES / kg is divided into two equal doses: the first part (30 PIECES / kg) is injected micro-jet into the CVC, the second dose (30 UNITS / kg) of heparin is diluted in 20.0 ml of a solution of NaCl 0.9% and used to “flush” the microcatheter at a rate of 10-20 ml / hour.

4) 2-3 minutes before a.ophthalmica catheterization, it is necessary to change the ventilation parameters in order to create moderate hyperventilation: the fraction of respirable oxygen FiO _{2 is} set to 100%, the pressure on inspiration of Pinsp is increased by 2-3 units.

5) During a.ophtalmica catheterization: at the time of the first respiratory movement with a decrease in lung volume / compliance (for example, the initial inspiratory volume is 101 ml, 15 seconds after the introduction of the microcatheter at the mouth of a.ophthalmica with each respiratory movement it is successively reduced to 80 ml, 70 ml, 50 ml, 30 ml), you must immediately perform the following steps:

a) inject 0.5 μg / kg (according to several studies - up to 1 μg / kg) of adrenaline with a bolus from perfuser and start timing;

b) increase the pressure on inspiration of Pinsp so that the tidal volume is not less than 50% of the initial (sometimes up to 22-38 cm water), increase the respiratory rate (BH) by 1.5 times;

c) control: blood pressure, heart rate, venous blood saturation (SpO ₂ ), tidal volume, plethysmogram form.

Positive dynamics will be manifested as follows - a gradual increase in tidal volume, normalization of the plethysmogram (return of a pronounced pulse wave), stable blood pressure, SpO ₂ - at least 90%. With positive dynamics, gradually return the ventilation parameters to the original;

d) In the absence of positive dynamics, a repeated bolus of adrenaline is produced. If a single-lumen CVC is used, it is necessary to ensure that the line with the adrenaline is washed with the infusion solution at a sufficient speed;

6) With a decrease in the level of average blood pressure (BPA) below perfusion (below 60 mm Hg) after bronchospasm resolves, hemodynamics are maintained by infusion of an adrenaline solution, adhering to the target values of blood pressure in a dose of 0.15 μg / kg / min.

Hemodynamics is assessed by monitoring blood pressure and heart rate during surgery at the stages of the beginning of the operation, surgical access and the end of the operation.

AD is considered pathological deviation _cp at ± 20 mm Hg. Art. taking into account the initial blood pressure _avg and the age norm of the patient.

The severity of the manifestations of the trigemino-pulmonary reflex, we evaluated as follows:

- weak: the occurrence of severe bronchospasm after a.ophthalmica catheterization, administration of adrenaline at a dose of 0.5 μg / kg once, the resolution of bronchospasm for 2-3 minutes, the saturation of venous blood does not decrease below 98%;

- moderate: the occurrence of severe bronchospasm after a.ophthalmica catheterization, the need for a double administration of adrenaline at a dose of 0.5 μg / kg and / or a short-term (up to 20 sec) episode of a decrease in saturation and venous blood of at least 90%;

With a mild to moderate degree of cardiorespiratory disorders, calcium preparations, for example, calcium gluconate and NSAIDs, are introduced before waking up for the purpose of postoperative analgesia, for example, analgin or perphalgan;

- severe: the occurrence of severe bronchospasm after a.ophthalmica catheterization - the need for twice or three times the administration of adrenaline 0.5 μg / kg and / or an episode of a decrease in saturation and venous blood below 90% for more than 20 seconds and / or a decrease in blood pressure by more than 20% of the original - the need for hemodynamic support (infusion of adrenaline solution).

7) If the second procedure of selective intra-arterial chemotherapy occurs, expressed and difficult to stop cardiorespiratory disorders in subsequent procedures after induction of anesthesia, retrobulbar blockade is performed under mechanical ventilation. Retrobulbar block is mainly used in ophthalmic surgery. And since the oculorespiratory reflex has the same afferent pathways as the oculocardial reflex, but is relayed in the area of respiration control, and the efferent impulses propagate along the phrenic nerve and other nerves involved in breathing, blocking the afferent limb of the reflex is used to stop these disorders using a retrobulbar [Dina Ahmed, MD. Updates in pediatric ophthalmic anesthesia. Anaesthesia, Pain & Intensive Care. 03/01/2014].

Under conditions of general anesthesia and mechanical ventilation, retrobulbar blockade is performed. To this end, after treating the skin with a local antiseptic, the 23G needle is inserted at a point 1/3 of the distance from the lateral to the medial corners of the palpebral fissure, perpendicular to the skin in the rear direction parallel to the bottom of the orbit, as shown in figure 1. After contact with the lower wall of the orbit, the needle is guided medianasally at an angle of 45 ° to enter the muscle cone and advance another 5 mm, but not deeper than 20 mm. If the needle is in a cone, air bubbles appear and a lack of resistance is noted [Local anesthesia: practical guide / M.F. Malroy et al .; trans. from English under the editorship of prof. E.A. Evdokimova. - 4th ed. - M .: BINOM, 2014]. After thorough aspiration, 1.0-1.5 ml of 0.5% ropivacaine solution is slowly introduced. With correctly performed RBF, the development of mydriasis is noted, as can be seen in figure 2.

The invention is illustrated by the following example:

Example No. 1.

1st procedure. Child S., 8 months old, weighing 9 kg, diagnosed with retinoblastoma of the right eye, was admitted to the operating room on January 17, 2018 for special treatment with the method of intra-arterial highly selective chemotherapy. 01/16/2018 Puncture and catheterization of the central vein with x-ray control.

Induction: Sevoflurane 7 vol. % in an oxygen stream of 7 l / min, fentanyl 0.005% - 1.0 ml, kruaron 5 mg w / w. Intubation orotracheal ETT No. 3,5 with a cuff without technical difficulties, a nasogastric tube was installed. A pneumoprotective mechanical ventilation with moderate hyperventilation was started in the Press Mode: P _insp = 16 cm H ₂ O, DO = 40 ml, NPV - 26 per min, PEEP = 4 cm water, FiO ₂ = 65%. Monitoring after induction: HELL = 90/60 mm Hg, heart rate = 116 per min, SpO2 = 99-100%, EtCO ₂ 28-30 mm Hg. Art. Maintenance of anesthesia: Sevoran 2.5-3% vol. Infusion therapy: sterofundin - 8 ml / kg / h. After puncture and catheterization by the femoral artery surgeon, heparin prophylaxis was started: 30 U / kg micro-jet in CVC, the second dose of 30 U / kg heparin in 20.0 ml of 0.9% NaCl solution in a micro-catheter at a rate of 20 ml / hour. 3 minutes before catheterization, a.ophthalmica FiO _{2 was} increased to 100%, and Pinsp inspiratory pressure was increased to 19 units.

During a.ophtalmica catheterization, a decrease in tidal volume to 35 ml was noted, to compensate for the decreased lung compliance, Pinsp inspiratory pressure was increased to 30 cm H ₂ O, NPV to 35 per min cm H ₂ O cm H ₂ O. 0.5 μg / kg of adrenaline was injected. bolus, dexamethasone 2 mg iv. Monitoring with the development of cardiorespiratory disorders: BP = 66/30 mmHg, heart rate = 86 min, SpO2 = 89%, EtCO ₂ 38-40 mm Hg. Art. Despite the administration of an adrenaline bolus, hypotension of arterial pressure cf. 36 mm Hg, which required the connection of a continuous infusion of r-r adrenaline at a dose of 0.15 μg / kg / min. Recovery time 260 sec. Monitoring after stopping cardiorespiratory disorders: BP = 106/50 mm Hg, heart rate = 158 per min, SpO2 = 98%, EtCO ₂ 36-38 mm Hg. Art. Before waking up for the purpose of analgesia, the following were introduced: analgin 0.1 ml iv.

After restoration of independent adequate breathing, the boy is extubated. The phenomena of incomplete laryngospasm were noted, stopped by the introduction of euphilin 2.4% - 1.0 ml IV bolus. The boy in a state of residual drug sedation was transferred to the intensive care unit under the supervision of a resuscitator.

When conducting the 2nd procedure of CIAHT in the same child, taking into account the pronounced reaction of cardiorespiratory disorders during the first procedure, it was decided to use the 7th element of the anesthetic management method for the selective delivery of a chemotherapy drug to the retina of the eye - retrobulbar block. 02.16.2018

After induction of sevoflurane 7 vol. % in oxygen flow 7 l / min, fentanyl injection 0.005% - 1.0 ml, croaron 5 mg iv, intubation ETT No. 3.5 with a cuff, pneumonprotective mechanical ventilation with moderate hyperventilation in Press Mode started: P _insp = 16 cm H ₂ O, DO = 40 ml, NPV - 26 per min, PEEP = 4 cm water, FiO ₂ = 65% retrobulbar blockade of 1.0 ml of 0.5% ropivacaine solution was performed. Maintenance of anesthesia: Sevoran 2.5-3% vol. Infusion therapy: sterofundin -8 ml / kg / h. After puncture and catheterization by the femoral artery surgeon, heparin prophylaxis was started: 30 U / kg micro-jet in CVC, the second dose of 30 U / kg heparin in 20.0 ml of 0.9% NaCl solution in a micro-catheter at a rate of 20 ml / hour. 3 minutes before catheterization, a.ophthalmica FiO _{2 was} increased to 100%, and Pinsp inspiratory pressure was increased to 19 units.

With a.ophtalmica catheterization, the development of cardiorespiratory disorders was not observed. A smooth course of anesthesia and the early postoperative period was noted.

At the Research Institute of Pediatric Oncology and Hematology, Federal State Budgetary Institution Scientific Research Center for Oncology named after N.N. Blokhina »Ministry of Health of Russia in children with retinoblastoma in 2013-2018 procedures were carried out to selectively deliver the chemotherapy drug to the retina (n = 517) under conditions of general anesthesia for the first time (n = 211), in 186 (88%) cases a smooth course of anesthesia was observed, deviations in blood pressure and heart rate did not exceed 20% of the initial values . In 25 (12%) cases, in patients who underwent the first time CIAHT procedure, 10-20 seconds after catheterization with the a.ophthalmica microcatheter, bronchospasm occurred with a decrease in tidal volume to 30% of the initial one. Patients who underwent repeated CIAHT procedure (2nd, 3rd session, etc.) (n = 306), in 177 (58%) cases, the clinical picture of trigemino-pulmonary reflex of various severity was manifested: mild - 127 / 177 (72%), moderate - 26/177 (15%), severe - 23/177 (13%). Improvement of anesthetic management during the CIAHT procedure allowed the treatment of children with a pronounced degree of reaction, including infants up to 6 months, as well as the prevention of trigeminopulmonary reflex and reduce its severity. For 2018, CIAHT was performed for 8 patients under the age of 3 months. Worldwide, the age of up to 6 months is a limitation for the selective delivery of chemotherapy to the retina of the eye. The use of the claimed method of treatment in 177 patients was not accompanied by the development of complications. Of these, 14 retrobulbar blockade was performed. In 29% of patients after retrobulbar blockade during the third CIAHT procedure, the development of cardio-respiratory disorders was not observed, in 71% there was a significantly lower increase in airway resistance and greater hemodynamic stability P _insp 25.4 ± 7.4 cm water ., against 33.8 ± 3.2 cm. Retrobulbar blockade can prevent postoperative pain, reduce the frequency of psychomotor agitation in patients after SIAHT.

Claims (1)

A method for providing anesthetic support for the selective delivery of a chemotherapy drug to the retina of the eye in the treatment of intraocular retinoblastoma in children, including the induction and maintenance of anesthesia with sevoflurane, muscle relaxation with rocuronium, heparin prophylaxis after puncture and catheterization of the femoral artery, the administration of dexamethrin and pneuminum, and the patient is required to preventive incremental increase in inspiratory pressure in the upper respiratory tract 3 min before a.opht catheterization halmica; after a.ophtalmica catheterization: at the time of the first respiratory movement with a decrease in lung compliance, 0.5 μg / kg of adrenaline is administered as a bolus, Pinsp inspiratory pressure is increased so that the tidal volume is not less than 50% of the initial one, the respiratory rate is increased by 1, 5 times; with a decrease in average blood pressure below 60 mm Hg after bronchospasm resolves, hemodynamics are supported by infusion of an adrenaline solution in a dose of 0.15 μg / kg / min; with a mild to moderate severity of the manifestations of the trigemino-pulmonary reflex, 10% calcium gluconate at a dose of 1.0 ml and analgin at a dose of 0.1 ml intravenously; in children with a pronounced degree of reaction during repeated procedures after induction of anesthesia, retrobulbar blockade is performed.

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