LITHUANIAN UNIVERSITY OF HEALTH SCIENCES VETERINARY ACADEMY
Faculty of Veterinary Medicine
Rebecka Anna Jambrisak
SIDE EFFECTS OF PREMEDICATIONS FOR CANINES WITH LIVER
AND KIDNEY DISEASES DURING GENERAL ANESTHESIA
ŠUNŲ, SERGANČIŲ KEPENŲ IR INKSTŲ LIGOMIS, PREMEDIKACIJOS
SUKELTAS ŠALTUINIS POVEIKIS BENDROSIOS NEJAUTROS METU
MASTER THESIS
of Integrated Studies of Veterinary Medicine
Supervisor: DVM, assist. Kristina Ramanauskaitė
THE WORK WAS DONE IN THE DEPARTMENT OF VETERINARY
SMALL ANIMAL CLINIC
CONFIRMATION OF THE INDEPENDENCE OF DONE WORK
I confirm that the presented Master Thesis “Side effects of premedications for canines with liver and kidney diseases during general anesthesia”.
1. Has been done by me;
2. Has not been used in any other Lithuanian or foreign university;
3. I have not used any other sources not indicated in the work and I present the complete list of used literature.
Rebecka Anna Jambrisak
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CONFIRMATION ABOUT RESPONSIBILITY FOR CORRECTNESS OF THE ENGLISH LANGUAGE IN THE DONE WORK
I confirm the correctness of the English language in the done work. Gunilla Wetterlöf
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CONCLUSION OF THE SUPERVISOR REGARDING DEFENCE OF THE MASTER THESIS
DVM, assist. Kristina Ramanauskaitė
(date) (Supervisor’s name, surname) (signature)
THE MASTER THESIS HAVE BEEN APPROVED IN THE SMALL ANIMAL CLINIC DEPARTMENT
(date of approval) (name, surname of the manager of (signature) department/clinic)
Reviewers of the Master Thesis
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Evaluation of defence commission of the Master Thesis:
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THE TABLE OF CONTENTS
SUMMARY ... 6 SANTRAUKA ... 7 ABBREVIATIONS... 8 INTRODUCTION... 9 1. LITERATURE REVIEW... 101.1 General anesthesia definition ... 10
1.2 Premedication for general anesthesia ... 10
1.2.1 Reasons and aims of premedication ... 10
1.2.2 Preanesthetic anxiolytic and sedatives ... 11
1.2.2.1 Phenothiazines (acepromazine) ... 11
1.2.2.2 Alpha-2-agonists (medetomidine, dexmedetomidine and xylazine) ... 11
1.2.2.3 Benzodiazepines (midazolam and diazepam) ... 12
1.2.3 Preanesthetic analgesic drugs ... 12
1.2.3.1 Opioids (fentanyl, morphine, methadone, buprenorphine and butorphanol) ... 12
1.2.4 Anticholinergic Agents (atropine and glycopyrronium) ... 13
1.2.4.1 Atropine... 14
1.2.4.2 Glycopyrrolate... 14
1.3 Premedication for patients with kidney disease ... 14
1.3.1 Preanesthetic considerations for patients with kidney disease ... 14
1.3.2 Recommended premedication for kidney disease ... 15
1.3.3 Drugs that are contraindicated ... 15
1.4 Premedication for patients with liver disease ... 16
1.4.1 Preanesthetic considerations for patients with liver disease ... 16
1.4.2 Recommended drugs to use ... 17
1.4.3 Drugs that should be avoided ... 17
1.5 Premedication side effects ... 17
1.5.1 Definition of side effects ... 17
1.5.2 Side effects for the most common used premedication ... 18
1.6 Induction, maintenance and monitoring ... 18
1.6.1.1 Common used induction drugs (injectable) ... 19 1.6.1.1.1 Propofol ... 19 1.6.1.1.2 Alfaxalone ... 19 1.6.1.1.3 Ketamine ... 19 1.6.2 Maintenance ... 19 1.6.3 Monitoring... 20
1.7 Induction, maintenance and monitoring for patients with kidney disease ... 21
1.7.1 Induction ... 21
1.7.2 Maintenance ... 21
1.7.3 Monitoring... 21
1.8 Induction, maintenance and monitoring for patients with liver disease ... 22
1.8.1 Induction ... 22
1.8.2 Maintenance ... 22
1.8.3 Monitoring... 22
1.9 Anesthetic complication ... 22
1.9.1 Cardiovascular System Complications ... 22
1.9.1.1 Bradycardia ... 22
1.9.1.2 Hypotension ... 23
1.9.1.3 Tachycardia ... 24
1.9.2 Respiratory System Complications ... 24
1.9.2.1 Hypoventilation ... 24 1.9.2.2 Hypoxemia ... 24 1.9.3 Thermoregulation complications ... 25 1.9.3.1 Hypothermia ... 25 1.10 Recovery period ... 25 2. METHODOLOGY ... 26
2.1 Patients health status evaluation... 26
2.2 General anesthesia ... 27
2.2.1 Patients premedication ... 29
2.2.1.1 Patients divided according to their premedications... 29
2.2.2 Induction ... 30
2.2.3 Maintenance ... 30
2.2.5 Recovery ... 31
2.3 Statistical analysis ... 31
3. RESULTS ... 32
3.1 SPSS results ... 32
3.1.1 p-value for Group I... 32
3.1.2 p-value for Group II ... 32
3.1.3 p-value for Group III ... 32
3.2 Descriptive statistics... 32
3.2.1 Descriptive statistics for Group I, Group II, and Group III ... 32
3.2.2 Descriptive statistics for Group I, and Group II, and Group III according to their premedications ... 33
3.3 Cardiovascular system parameter (HR and MAP) for Group I, Group II, and Group III ... 34
3.4 Respiratory system parameters (RR) for Group I, Group II, and Group III ... 40
3.5 Thermoregulation parameters (temperature) for Group I, Group II, and Group III... 41
4. DISCUSSION ... 44
4.1 Premedication side effects to cardiovascular system ... 44
4.2 Premedication side effects to the respiratory system ... 45
4.3 Premedication side effect on thermoregulation system ... 45
4.4 Safest premedication ... 45
CONCLUSIONS ... 47
SUGGESTION AND RECOMMENDATION... 48
REFERENCES ... 49
SIDE EFFECTS OF PREMEDICATIONS FOR CANINES WITH LIVER AND KIDNEY DISEASES DURING GENERAL ANESTHESIA
Rebecka Anna Jambrisak Master Thesis
SUMMARY
Having a comprehensive knowledge of the effects anesthesia drugs have on patients with liver and kidney diseases is necessary since it can reduce the anesthesia mortality of these patients.
This study aims to identify and evaluate different side effects of premedications for patients with liver and kidney diseases during general anesthesia.
The objectives are to evaluate the side effects of different premedication protocols and how they can affect the cardiovascular, respiratory, and thermoregulation system for patients with liver and kidney diseases during anesthesia. Also, to choose the safest premedication plan for patients with liver and kidney diseases.
This research work was carried out in Evidensia Specialistdjursjukhuset (Helsingborg, in Sweden). The collection of the data was carried out in June until August 2019 and in January 2020. The total sample consists of 24 dogs from the three different groups: I group - 9 healthy dogs (n=9), II Group - 9 dogs with liver diseases (n=9), and III Group - 6 dogs with kidney diseases (n=6). The different premedication drugs were used for premedication and analysed to see how they affect the cardiovascular, respiratory, and thermoregulation system in patients with kidney and liver diseases. The results of this study show no significant difference in the parameters HR, SpO2, MAP, RR, and
Temp (p > 0.05).
In the III group the most common complications were bradycardia, hypotension, tachypnea, and hypothermia for the patients that were premedicated with dexmedetomidine hydrochloride, methadone, and maropitant (subgroup 2) (p>0.05).
In the II group the most common complications were hypertension for patients that were premedicated with methadone and diazepam (subgroup 3), and bradypnea for patients that were premedicated with medetomidine hydrochloride (subgroup 2) (p>0.05).
The safest premedication plan for patients with kidney diseases is benzodiazepines in combination with opioids. For patients with liver diseases, the safest premedication plan is opioids alone, or opioids together with midazolam in a low dose for patients with mild to moderate liver disease.
ŠUNŲ, SERGANČIŲ KEPENŲ IR INKSTŲ LIGOMIS, PREMEDIKACIJOS SUKELTAS ŠALTUINIS POVEIKIS BENDROSIOS NEJAUTROS METU
Rebecka Anna Jambrisak Magistro baigiamasis darbas
SANTRAUKA
Išsamios žinios apie bendrosios nejautros metu premedikacijai naudojamas medžiagas ir jų poveikį įvairioms pacientų, sergančių inkstų ar kepenų ligomis, organų sistemoms gali ženkliai sumažinti šių pacientų mirtingumą dėl sukeliamos bendrosios nejautros ir jos pasėkoje išsivysčiusių komplikacijų.
Šiuo tyrimu siekta nustatyti ir įvertinti skirtingus premedikacijų šalutinius poveikius pacientams, sergantiems kepenų ir inkstų ligomis bendrosios nejautros metu.
Tyrimo uždaviniai yra: įvertinti šalutinius reiškinius bei poveikį širdies ir kraujagyslių, kvėpavimo bei termoreguliacijos sistemoms anestezijos metu pacientams, sergantiems kepenų ir inkstų ligomis, kai premedikacijai naudoti skirtingi medikamentų deriniai. Taip pat identifikuoti saugiausią premedikacijos metodą pacientams, sergantiems kepenų ir inkstų ligomis.
Tiriamasis darbas atliktas Evidensia Specialistdjursjukhuset (Helsingborgas, Švedija) veterinarijos klinikoje nuo 2019 m. birželio iki 2020 m. sausio mėn. Bendra tyrimo imtis - 24 šunys – suskirstyti į 3 grupes: I grupė – 9 sveiki šunys (n=9), II grupė – 9 šunys, sergantys kepenų ligomis (n=9), III grupė – 6 šunys, sergantys inkstų ligomis (n=6). Tyrimo metu analizuoti pacientų fiziologiniai rodikliai operacijos metu, premedikacijos protokolai, šių vaistų poveikis širdies ir kraujagyslių, kvėpavimo bei termoreguliacijos sistemoms.
Statistiškai reikšmingas ryšys tarp širdies susitraukimų dažnio, deguonies įsotinimo kraujyje, vidutinio arterinio kraujo spaudimo, kvėpavimo dažnio ir kūno temperatūros tarp grupių nenustatytas (p>0,05).
III grupės pacientams, kurie buvo premedikuoti deksmedetomidino hidrochloridu, methadonu, ir maropitantu, buvo bradikardija, hipotenzija, tachipnėja, ir hipotermija (2 pogrupis) (p>0.05).
II grupės pacientams, premedikuotiems nuodojant metadoną, ir diazepamą, dažniausios komplikacijos buvo hipertencija (3 pogrupis), o pacientams premedikuotiems medetomidino hidrochloridu- bradipnėja (2 pogrupis) (p>0.05).
Saugiausias premedikacijos planas pacientams, sergantiems inkstų ligomis, yra benzodiazepinai derinyje su opioidais, o pacientams, sergantiems kepenų ligomis- vien opioidai arba opioidai derinyje su maža midazolamo doze.
Raktiniai žodžiai: anestezija, šunys, premedikacija, pašaliniai poveikiai, kepenų ligos, inkstų ligos.
ABBREVIATIONS
ABP- Arterial blood pressureALP- Alkaline phosphatase ALT- Alanine aminotransferase
APTT- Activated partial thromboplastin time BP- Blood pressure
Bpm- Beats per minute BUN- Blood urea nitrogen C- Degree Celsius
CNS- Central nervous system CO- Carbon monoxide CO2-Carbon dioxide CRT- Capillary refill time EtCO2- End tial carbone dioxide
ETiso- The end-tidal isoflurane concentration GFR- Glomerular filtration rate
HR- Heart rate IM- Intramuscular
IPH- Inadvertent perianesthetic hypothermia Iso- Isoflurane
IV- Intravenous
MAP- Mean arterial blood pressure Max- Maximum
Min- Minimum
mmHg- Millimeter of mercury
NSAID- Nonsteroidal anti-inflammatory drugs O2- Oxygen
PT- Prothrombin time
PTT- Partial thromboplastin time RR- Respiratory rate
SC- Subcutaneous
SpO2- Saturation of peripheral oxygen
Temp- Temperature
INTRODUCTION
The anesthesia-related mortality risk in healthy dogs is 0.05-0.1 % and in the ill dogs 1.33 % (1–3).
The first aim when performing anesthesia in an unwell patient must be to optimize tissue perfusion and enable sufficient oxygenation of the vital organs in particular while achieving analgesia, muscle relaxation, and unconsciousness in the patient. The final aim of the treatment is to provide maximum physiological function, rather than the measured parameters returning to normal. Values that are considered normal for healthy patients undergoing anesthesia produce higher rates of mortality in unhealthy patients (4).
Anesthesia is achieved via the controlled administration of drugs with toxic properties to the patient and has a risk to cause organ dysfunction, delayed recovery, and death. Safe anesthesia needs careful monitoring and good knowledge of the effects of various anesthetic drugs on different organ systems (4).
Therefore, this study is needed to improve the knowledge of the effects of drugs in patients with liver and kidney diseases. With provided and in novel information for anesthesia protocol to patients with liver and kidney diseases is lacking.
The aim of the present study: to identify and evaluate different side effects of premedications for dogs with liver and kidney diseases during general anesthesia.
The objectives of the present study are to evaluate:
1. Evaluate different premedication protocols side effects on the cardiovascular system for patients with liver and kidney diseases during general anesthesia.
2. Evaluate different premedication protocols side effects to the respiratory system for patients with liver and kidney diseases during general anesthesia.
3. Evaluate different premedication protocols side effects on the thermoregulation system for patients with liver and kidney diseases during general anesthesia.
1. LITERATURE REVIEW
1.1 General anesthesia definition
The term anesthesia, from the Greek term anaisthaesia means “insensibility”, and is used to describe the loss of sensation to the entire or parts of the body. Anesthesia is induced by drugs that cause depression to the activity of nervous tissue either locally, regionally or within the central nervous system (C) (5).
General anesthesia is drug-induced, and cause unconsciousness and is characterized by controlled but reversible depression of the CSN and perception. The patient in this state is not arousable by noxious stimulation, and the sensory, motor and autonomic reflex functions are affected in various degree depending on the specific drug and techniques which is used (6).
1.2 Premedication for general anesthesia
The administration of drugs prior to anesthetic induction is called preanesthetic medication and is a part of the general anesthesia. Drugs that include in preanesthetic medication are tranquillizers/sedatives (phenothiazine, benzodiazepines, alpha-2 adrenoceptor agonists), analgesics (opioids, NSAIDs), and anticholinergics (atropine, glycopyrrolate) (7).
Safe and effective anesthesia of dogs rely on preanesthetic patient assessment and preparation. Patients should be premedicated with drugs that provide sedation and analgesia prior to anesthetic induction with drugs that allow endotracheal intubation (8).
1.2.1 Reasons and aims of premedication
The reasons for preanesthetic medications include:
• Provision of a chemical restraint (i.e. sedation for catherization and control of animal for handling); • Reduce of anxiety in the animal, leads to reducing of catecholamines and the risk of arrhythmias during anesthetic induction and maintenance (7).
• The total dose of anesthetic induction and maintenance requirements reduces; • Provided analgesia is included in the premedication, such as NSAID and opioids; • Reductions of bradycardia, salivation and airways secretions (7),
The aims of premedications drugs used in dogs should ideally: • Produce sedation and anxiolysis;
• Produce analgesia;
• Have minimal effects on the cardiovascular system; • Cause minimal respiratory depression;
• Reduce the side effects of other anesthetic drugs; • Provide smooth and quiet recovery (9).
The drugs used for premedication does not achieve all the characteristics mention above, therefore it is recommended to use an anesthesia protocol, and combination of drugs with different specific effects that allow the dosages of individual drugs to be reduced. It can reduce the side effect and at the same time increase the sedation achievement (9).
1.2.2 Preanesthetic anxiolytic and sedatives
The benefits of preanesthetic anxiolytic and sedatives include decreased stress/anxiety and dose reduction of induction and maintenance drugs, which have dose-dependent adverse effects (10). Preanesthetic medications can be administered intramuscular (IM) or subcutaneous (SC) route, to achieve good effects in advance of anesthesia induction. Intravenously (IV) can be administered for acute dose-sparing effects of induction drugs. Specific drug/drugs combination should be based on their effects and on the individual patient needs (10).
1.2.2.1 Phenothiazines (acepromazine)
Phenothiazines (acepromazine) are dopamine antagonists and have calming, antipsychotic and mood-changing effects (9).
Provide mild sedation at the dose 0.01-0.05 mg/kg (even up to 0.1mg/kg) IM, a lower dose is given when it is IV (half of the IM dose), the oral dose is 1 mg/kg but can vary from 0.25-3 mg/kg for dogs. Takes 30-40 minutes for sedation to develop, and last for 3-4 hours but can persist for about 6-8 hours (11). The main adverse effect of acepromazine is decreased systemic vascular resistance and blood pressure (6).
Acepromazine is an antagonist of alpha1- adrenoreceptors, and can therefore cause peripheral
vasodilation and an increase in arterial blood pressure. Clinical doses of acepromazine have minimal effect on the respiratory function. Acepromazine cause a decrease in body temperature, because of peripheral vasodilation (9).
1.2.2.2 Alpha-2-agonists (medetomidine, dexmedetomidine and xylazine)
Alpha-2-agonists are sedative drugs with analgesic and muscle relaxant properties. The sedative effects take over the analgesic effects, the effects become apparent 5 minutes after administration and the maximal sedation takes up to 20 minutes to be achieved. The duration of the sedation is dose-dependent, but last between 30-60 minutes (11).
The licensed drugs for small animal use are medetomidine hydrochloride (Domitor) 1mg/ml, Dexmedetomidine hydrochloride (Dexdomitor) 0,5 mg/ml and Xylazine (Rompun) 20 mg/ml (11).
Dexdmedetomidine hydrochloride provides reliable sedation, analgesia, and chemical restraint in dogs (12). The most common side effects of small animals include decreased cardiac output and initial hypertension. The advantage of dexmedetomidine as sedation is the availability if an antagonist to provide rapid recovery from sedation (13).
When medetomidine hydrochloride is administered some cardiovascular effect can be shown, higher doses cause more potent coronary artery vasoconstriction, while sedation and analgesia are dose dependent. Coronary vasoconstriction occurs in dogs that have been given dexmedetomidine hydrochloride (14).
The main negative cardiovascular effects of all alpha-2-agonists include bradycardia, reduce in cardiac output and increase in systemic vascular resistance (15).
1.2.2.3 Benzodiazepines (midazolam and diazepam)
Benzodiazepine compounds (diazepam and midazolam) exert their main sedative effects through depression of the limbic system, and it does not have analgesic properties (6).
Benzodiazepines administered alone produce minimal or no sedation in healthy dogs, and is therefore given in combination with other sedatives. It is common to combine benzodiazepine with an opioid to support the cardiovascular system (9).
The dose for diazepam and midazolam is 0.1-0.25 mg/kg IV for dogs (11).
Higher doses in dogs of diazepam may have adverse effects on cardiac contractility and cardiac output (16).
1.2.3 Preanesthetic analgesic drugs
Analgesia is a component of general anesthesia, and has numerous advantages (10). First, analgesia makes the anesthesia more safe by reducing the dose of inhalant drugs that are needed for anesthesia maintenance, and it will decrease the adverse effects such as hypotension and hypoventilation which are dose-dependent (17).
Second, analgesia improves patient outcome with less pain-related adverse effects such as tachycardia, hypertension, slowed gastrointestinal motility, and prolonged wound healing (18).
Using multiple drugs and modalities, each with activity at different sites of the pain pathway will eliminate pain at multiple sites and from multiple sources, this concept is known as multimodal or balanced analgesia. This will provide a greater pain relief and promote anesthesia safety by reducing the required anesthesia drug dosage (18).
Opioids are often the first choice when designing an anesthesia protocol, but is more effective if it is centered on anti-inflammatory drugs (NSAID) and local anesthetic drugs when analgesic protocols are made. NSAID should be administered to all appropriate patients. Because inflammation is the pathology that produces most acute pain syndrome, therefore is important to control the inflammation to decrease further tissue damage and speeds healing (10).
1.2.3.1 Opioids (fentanyl, morphine, methadone, buprenorphine and butorphanol) Opioids do not block pain at it is a source or stop the transmission pain, but they are strong and rapidly acting which make them excellent for acute pain relief (19).
Opioids are commonly incorporated into premedication to provide analgesia and to improve the reliability and intensity of the sedation achieved following the combination with the primary sedative drug. The choice of opioids depends on the degree of analgesia is needed, and the speed of the action of the drugs (9).
Table 1. Opioids selection considerations (10)
1.2.4 Anticholinergic Agents (atropine and glycopyrronium)
Anticholinergic agents (atropine and glycopyrronium) are used to prevent unwanted effects of stimulation of the parasympathetic nervous system by anesthetic agents or surgery (9).
Anticholinergics remain an important and vital adjunct to anesthesia, but should be used with carefulness and based on a specific indication and need (20).
Indications of anticholinergics agents during anesthesia include: - Reduction of salvation during oral and dental surgeries;
- Bronchodilation effect;
- Block vagovagal reflexes during surgeries that stimulate this reflect (ocular surgery); - Prevent bradycardia associated with some opioids (for example butorphanol used as premedication in a young fit dog or use of fentanyl as a bolus or infusion during anesthesia); - Treatment of AV block conduction disturbance;
- To maintain heart rate in the patient whose cardiac output is critically rate dependent (20).
Opioid Analgesia Duration Adverse effects Dose (mg/kg)
for canine Fentanyl (50 g/ml) Profound analgesia Full mu and kappa agonists
20-30min Less likely to cause adverse effects that other full opioid agonists. 0.001-0.005 IV Morphine (10mg/ml) Profound analgesia Full mu and kappa agonists 2-4 hr.
Adverse effects are minimal; may cause vomiting after IM injection, histamine release if administered fast IV,
bradycardia and respiratory depression.
0.25-1.0 IM, IV
Methadone (10mg/ml)
Similar to morphine, but no histamine release and little to no vomiting. 0.4 IV, 0.2-0.6 Buprenorphine (0.3 mg/ml) Moderate analgesia Partial mu agonist
4-8 hr. Same adverse effects as other opioids but milder.
0.01-0.03 IM, IV Butorphanol (10mg/ml) Mild-moderate analgesia Kappa agonist, mu antagonist
20-60min Same adverse effects as other opioids but milder.
1.2.4.1 Atropine
Atropine is a natural alkaloid and a tertiary amine. Dose in dogs is 0.01-0.04mg/kg IV (11). Atropine block vagotonic effects on the heart, causing tachycardia. Increasing heart rate with anticholinergic drugs may not increase cardiac output, but it does increase myocardial oxygen consumption and therefore increase myocardial workload (20).
1.2.4.2 Glycopyrrolate
Glycopyrrolate is a synthetic quaternary ammonium compound and is also known as glycopyrronium. Dose is 5-10g/kg IV (11).
Glycopyrrolate is used to manage bradycardia and vagally mediated arrhythmias and to reduce oral and airway secretions. The effect includes a decrease of oral secretions, increase of heart rate, an increase of gastric PH, a decrease of gastrointestinal motility and ocular effects (21).
1.3 Premedication for patients with kidney disease
Renal diseases are common in dogs, in one study the mortality from renal disease in dogs was 5 percent (22). Almost every anesthetic agent decreases the glomerular filtration rate (GFR), and renal blood flow. Therefore, general anesthesia should not be considered for patients with preexisting renal disease. If the general anesthesia may be necessary for such patient, the step should be taken to minimize any detrimental impact to remaining nephron function. General agents and adjuncts that optimize cardiac output are the best choices for the patient with renal disease. Blood pressure monitoring is very valuable to manage renal blood flow and fluid therapy (23).
1.3.1 Preanesthetic considerations for patients with kidney disease
Patients with kidney pathologies can be present with varying degrees of physiologically compensated kidney dysfunction. The degree of kidney dysfunction determines the level of the physiological disturbance of the kidney and the anesthetic risk to the patient. The kidney dysfunction is commonly result from altered fluid, electrolyte balance and acid-base disturbances (24).
Preoperative assessment of the patient with kidney dysfunction should be based on clinical history, physical examination and analysis of laboratory data. Fluid therapy for one or two hours before surgery is recommended, such as lactated Ringer solution should be given intravenously (24). If the patient has severe renal dysfunction, is common to have acid-base disturbance such as metabolic acidosis. If it is moderate metabolic acidosis intravenous therapy containing bicarbonate precursor can be given, and severe metabolic acidosis intravenous therapy with sodium bicarbonate is recommended (24).
Patient with hyperkalemia can be treated by the intravenous administration of potassium-free solution such as normal saline or 5 % dextrose in water. The serum potassium concentration should be monitored carefully to avoid hypokalemia (24).
Anemia should be identified and assessed before general anesthesia (23). Patients that are anemic (hematocrit < 20 %) or hypoproteinemia (total serum protein < 3,5 g/dl) as a result of chronic kidney disease, may require blood transfusion with cross-matched fresh whole blood or plasma (24).
1.3.2 Recommended premedication for kidney disease
Anesthetic premedication is important in patients with kidney disease, to avoid stress and pain which can lead to sympathetic catecholamine release with resulting vasoconstriction and a decrease in renal blood flow. Premedication will decrease the amount of general anesthesia that is required and will improve the cardiac output and blood flow (25). The use of sedatives and analgesics will decrease the amount of induction and maintenance agents that are necessary for general anesthesia, which have potential to decrease cardiac output and reduce GFR and renal blood flow (23).
Acepromazine can create systemic hypotension due to vasodilation a result of its alpha-adrenergic blockade effect, and the alpha blockade may protect the renal cortex from
sympathetically mediated vasoconstriction. It is recommended to use a low dose of acepromazine (0.01-0.02 mg/kg) in patients that have been adequately fluid loaded (25).
The benzodiazepines (midazolam 0.2 mg/kg IM or IV, or diazepam 0.2 mg/kg IV), can be used for tranquilization and muscle relaxation in patients with renal disease(23,26).
Midazolam and diazepam have minimal cardiovascular effects and have therefore less effect on renal blood flow (25). Opioids are recommended for renal patients and are helpful for pain management (27). Opioids have minimal effect on the cardiovascular system with only a small portion excreted via the kidneys. The analgesia it provides will help to decrease pain related to sympathetic catecholamine injury to the kidneys (25).
Full mu agonists such as hydromorphone, fentanyl, morphine, or oxymorphone can be useful before, during and after anesthesia for pain relief. Butorphanol a kappa agonist and mu antagonists can be used if the anticipated pain is not great. Buprenorphine is a long-lasting partial mu agonist that can be considered for patient with renal disease (23).
The best choice is a combination of a pure agonist opioid and benzodiazepine (25). 1.3.3 Drugs that are contraindicated
Alpha-2 agonists (xylazine, dexmedetomidine) are not recommended for renal patients, because of the reduction in cardiac output and decrease in vital organ blood flow associated with their use, and medetomidine has been shown to reduce in GFR dogs. Patients with urinary tract obstruction should avoid alpha-2 agents, because it inhibits antidiuretic hormone which results in increased urine volume (25).
NSAID should be avoided in patients with renal failure (27). NSAIDs can negatively affect kidney function because of their ability to suppress homeostatic renal prostaglandins (28).
1.4 Premedication for patients with liver disease
Disorders of the liver are an important cause of morbidity and mortality in dogs (29). The liver plays an important role in maintaining hemostasis, and liver-associated hemostatic abnormalities have also been reported in veterinary medicine. 93 percent of dogs with naturally occurring hepatic disease have at least one abnormal coagulation test result value. 50 percent with an abnormal prothrombin time (PT) and activated partial thromboplastin time (APTT) (30).
Maintenance of adequate blood flow and oxygen delivery during general anesthesia is critical to reducing further damage to hepatocytes. Anesthetics and adjuncts should be chosen to support vital organ blood flow, and they should be expected to have a longer duration of effect in patients with liver disease (23).
Liver failure may result in disseminated intravascular coagulation, Hemostasis (PT, partial thromboplastin time (PTT), bleeding time) should be evaluated before general anesthesia is performed in patients with significant liver disease, especially if the surgery is planned (23).
1.4.1 Preanesthetic considerations for patients with liver disease
Patients with mild liver disease has less problem with general anesthesia than patient with severe or fulminant disease. Most common signs of liver dysfunction are hypoglycemia, hypoalbuminemia, high ammonia levels and high serum bile acids. This patients with these signs should be considered at greater risk for complications associated with general anesthesia (23). Patients with liver dysfunction may be unable to generate adequate body heat, which can lead to hypothermia and slow metabolism and result in prolonged recovery (27).
Patients with liver disease need preoperative blood work, to assess blood glucose, protein levels, blood coagulation time and electrolytes. The patients need to be closely monitored during intraoperatively and during recovery. It is necessary to use agents with short half-lives, minimal cardiovascular effects, and does that can be reversed (31).
The arterial blood pressure should be maintained > 70 mmHg to prevent further liver damage, hepatic ischemia and to aid in drug metabolism (31).
Can also be good to measure the serum chemistry such as Serum alanine aminotransferase (ALT) - it can be used to indicate liver cellular damage. Alkaline phosphatase (ALP) and blood urea nitrogen (BUN) are indicators of hepatic integrity and elevated enzymes indicate potential liver dysfunction (27).
Lactulose administration and enemas can be performed to help reduce ammonia levels in the body. To minimize further liver damage techniques and drugs that support liver function including vital organ blood flow and oxygen delivery should be used. It is important to maintain arterial carbon dioxide level, because hyperventilation and hypoventilation can result in a decrease in hepatic blood
flow. The blood glucose concentrations should be carefully monitored, if the concentration is low 2,5 % dextrose or crystalloid isotonic fluid can be given (23).
Patients with hypoalbuminemia and/or hypoproteinemia should avoid drugs with high protein binding. To avoid further dilution of blood protein, colloids can be added to the fluid therapy plan. If the patients have severe hypoalbuminemia or clotting disorder plasma transfusion may be needed (23).
1.4.2 Recommended drugs to use
Tranquilizer and sedative selection for the patient with liver disease is a challenge for the anesthetist. Some clinicians consider benzodiazepines worsen the problem with hepatic encephalopathy in patients with liver disease and recommend to avoid their use, and other consider them helpful and appropriate use choice for patients with mild to moderate disease (23). Midazolam may be preferred as it is water soluble whereas diazepam can cause vessel irritation and hypotension when given IV because of the propylene glycol carrier (25).
Benzodiazepines should be given in a low dose for patient with mild to moderate liver disease (26). Opioids although dependent on the liver for metabolism tend to be a good choice for patient with liver disease. The opioid selection should be based on patient analgesic needs, depending on the duration of the effect and route of administration (23).
1.4.3 Drugs that should be avoided
Acepromazine and alpha-2 adrenergic agonists should be avoided in patients that have moderate to severe liver disease. The liver plays the major role to eliminate acepromazine from the body in a healthy patient, therefore in a patient with liver disease the action is prolonged. Alpha-2 agents such as xylazine or dexmedetomidine compromise vital organ blood flow and oxygen delivery, therefore their use should be limited in patients with mild liver dysfunction (23).
1.5 Premedication side effects
1.5.1 Definition of side effects
Adverse drug reaction has been defined as a response to a drug that is harmful and unintended and occurs at doses normally used for prophylaxis, diagnosis or therapy of disease, or for modification of physiological function. The terms adverse effect and adverse reaction are interchangeable, except that and adverse effect are seen from the point of the drug, whereas an adverse reaction is seen from the point of view of the patient. The term adverse effect is preferable to other terms such as toxic effect and side effect, a side effect is related to the pharmacological properties of the drugs (32).
1.5.2 Side effects for the most common used premedication
Safe anesthesia requires careful monitoring and good knowledge of the effects of several anesthetic drug on different organ systems. The safest way to use anesthesia in critical patients is to select drugs whose effects are easily reversible and be careful with the dosage (4).
Phenothiazines (acepromazine) and alpha-2 agonists (xylazine, medetomidine, dexmedetomidine) have hyposensitive effects, and suppressing the cardiovascular system therefore these drugs are unsuitable for patients that are either unstable or hypotensive (33,34). Dexmedetomidine a potent alpha-2 agonist, can cause side effects such as vomiting, peripheral vasoconstriction, and hypertension, and reflex bradycardia may then be seen secondary to hypertension (35).
Benzodiazepines, and opioids have minimal side effects, in case of severe cardiovascular, respiratory or neurological depression these drugs can cause patient instability or prolonged sedation (33). The effects of benzodiazepines are antagonized by using flumazenil, and the effect of opioids can be reversed by using antagonists such as naloxone (4,33).
1.6 Induction, maintenance and monitoring
1.6.1. Anesthetic Induction
After pre-medication has had time to set in, induction can begin. IV injection is usually the preferred method, other inductions methods include intramuscular injection or mask induction (36).
IV induction allows for rapid airway control and allows for titration of the induction drug to affect within the given dosage range, unhealthy patients will require less dosage than healthy patients. A patient response to premedication can influence the amount and type of induction drug needed. Mask or chamber inductions can cause stress, delayed airway control and environmental contamination. To minimize the exposure to the personnel, adequate room ventilation is needed (8). The endotracheal tube and laryngoscope should be available to establish and maintain the patient airway soonest as possible. It is recommended to the largest diameter endotracheal tube that will easily fit through the arytenoid cartilages without damaging them, this will reduce the resistance and the work of breathing (37). The cuff should be inflated enough to create a seal for adequate positive pressure ventilation, over-inflation may cause tracheal damage (38). The tracheal intubation should be properly performed and maintained, it is an essential part of maintaining an open and protected airway. Apply corneal lubricant to protect the eyes from corneal ulceration during postinduction (8). Propofol is a preferred drug for IV induction, it provides a smooth induction and rapid recovery, there is some undesirable side effect such as the potential for apnea during the initial moments and some patients can get twitching of the limbs, and it will be some cardiovascular depression too (36).
1.6.1.1 Common used induction drugs (injectable) 1.6.1.1.1 Propofol
Propofol (2,6-diisopropylphenol) is a nonbarbiturate sedative/hypnotic drug, that is rapidly metabolized in the animal. The advances of this drug include the rapid induction of anesthesia, short duration of action, lack of excitatory side effects on induction and recovery and no significant effect on repeated administration (39).
Propofol at therapeutic doses causes significant decreases in heart rate, mean arterial pressure, and reductions in end-systolic elasticity, indicating a direct negative inotropic effect (40). Respiratory depression and apnea are important side effects in animals that receiving IV propofol. Propofol is a suitable choice in a patient with preexisting liver or kidney disease. Because it is highly lipophilic and rapidly metabolized primarily to inactive glucuronide conjugates, the metabolites being excreted in the urine (39).
Dose: 2-6mg/kg IV(10). 1.6.1.1.2 Alfaxalone
Alfaxalone is a synthetic neuroactive steroid that interacts with GABA receptor, it produces anesthesia and muscle relaxation (41). It rapidly metabolizes and eliminates from the body. Alfaxalone like propofol has dose-dependent changes such as hypoventilation and apnea, but has a wide margin of safety (42).
Dose: 1-3 mg/kg IV (10). 1.6.1.1.3 Ketamine
Ketamine is a phencyclidine derivative, and N-methyl-D-aspartate receptor antagonist. Ketamine has analgesic and anesthetics properties, and causes an increase in heart rate and arterial blood pressure as a result of the increased sympathetic efferent activity (39).
Animals with renal dysfunction have prolonged sleep time when larger doses of ketamine are given. Ketamine should be given cautiously to the animal that has significant hepatic or renal dysfunction (39). Ketamine used alone causes muscle rigidity and could potentially cause some type of seizures and tachyarrhythmias. These effects are alleviated if it is used together with the benzodiazepine (10).
Dose: 2-5mg/kg IV (10). 1.6.2 Maintenance
Once the patient is successfully induced and intubated, the patient should be attached to the anesthetic machine and the depth of anesthesia assessed by checking heart and respiratory rate, as well as reflexes and capillary refill time (CRT). An anesthetic monitoring chart should be used throughout the procedure (36).
Anesthesia is maintained by using inhalant anesthetics, but it can also be achieved with a continuous infusion or intermittent doses of injectable agents or a combination of injectable and inhalant drugs. For an safe and effective administration of inhalant anesthesia, and O2-enriched gas mixture is necessary (40,43).
Short-duration maintenance can be achieved with IM administration of sedatives together with ketamine. IM administration of alfaxalone can be effective for short-duration, and for deep sedation in cats and small dogs. But the high dose that is needed to receive anesthesia maintenance in healthy cats can cause hypermetria and excitement in the recovery (44).
The requirements for the ideal inhalation anesthetic agent include; explosive, non-inflammable, stable in storage, have a boiling point that enables suitable vaporization at room temperature, low solubility coefficients in blood and tissues such as fat to enable rapid induction of and recovery from anesthesia, pleasant smell and be non-irritant to the airways, not cause cardiopulmonary depression and provide good quality anesthesia (45).
Isoflurane or sevoflurane agents are the most commonly used inhalant agents. These agents create dose-dependent myocardial depression, hypotension, and respiratory depression. They have a rapid onset and recovery time, and allowing for rapid change in anesthetic concentration (42).
1.6.3 Monitoring
It can be critical after the drugs that are used for maintenance (i.e., injectable or inhalant) has been given, therefore it is important to careful monitoring, interpretation of physiologic changes, and response to patient physiologic changes with help of a well-trained anesthetist. Monitoring reduces the odds of anesthetic death, whereas lack of monitoring increases the odds of anesthetic death (2,46). Multiparameter electronic monitors and hands-on assessment of the patient by an anesthetist should be used, and treatment decisions should be based on the information from the electronic monitors and from the anesthetists assessment (10).
Monitoring of the cardiovascular function includes heart rate (HR), blood pressure (BP), rhythm (ECG), capillary refill time (CRT), mucous membrane colour, and pulse oximetry (SpO2).
Respiratory function monitoring includes respiratory rate (RR), oxygenation (percentage of haemoglobin saturated with oxygen (SpO2), and ventilation (ETCO2). Monitoring of anesthetic
depth includes absent of palpebral reflex, mild jaw tone (i.e., muscle relaxation), and lack of purposeful movement (10). Thermal support and monitoring of body temperature should be provided throughout the perianesthetic period (8). O2 should be given to the patient, the O2 flow rates depend
on the breathing circuit (10). Nonrebreathing circuit is used for small dogs (patients < 3-5 kg), and the O2 should be approximately 200-400 ml/kg/min. Rebreathing circuits (i.e., circle systems) are
typically used in patients > 3-5 kg, and during maintenance phase total O2 flow rate should be 20-40
circuit, a relatively high flow rate (2-3 l/min) should be given if a rapid change in the anesthetic depth occurs, such as during the transition from injectables (induction) to inhalants or at the end of the procedure (discontinuing inhalants). Nonrebreathing circuit has a high oxygen flow, therefore is no need to increase the flow at induction and after discontinuing (10).
After induction and intubation the patient may be apneic or have shallow respiratory rate, then required intermittent (1-4 breaths/min) positive pressure ventilation breath should be delivered by the anesthetist until the respiratory depression of the induction drugs subsides (10).
Balanced crystalloid fluids should be administered to patients that undergo anesthesia, and the basal fluid rate for healthy dogs is 5 ml/kg/hr. and 3 ml/kg/hr. (47).
1.7 Induction, maintenance and monitoring for patients with kidney disease
1.7.1 Induction
The choice induction drug is not critical in patients with compensated renal disease, but the patients who are severely depressed should have an anesthetic plan that maximizes cardiac output and stability (23). Propofol, has been shown to have minimal effects on GFR. Propofol induction with a constant-rate infusion may be helpful in patients that need chemical restraint while measuring GFR (23).
1.7.2 Maintenance
Isoflurane and sevoflurane will maintain renal blood flow better than halothane, and these agents decrease GFR. The use of opioid constant-rate infusion, regional or local anesthesia and use of premedication will help to decrease the amount of needed inhalant (23).
1.7.3 Monitoring
Careful attention should be paid to blood pressure monitoring to help ensure that the kidneys are adequately perfused and have sufficient blood flow to support the remaining nephrons. Acid-base status is important in animals with kidney disease, because animals with acute renal disease are at risk of electrolyte abnormalities such as hyperkalemia (23).
Mean arterial blood pressure should be maintained above 60 mmHg to provide sufficient blood flow to vital organs. Mean arterial pressures above 70 mmHg are suitable if the renal disease is present. Systolic blood pressure should be maintained above 90 mmHg. Patient with the
compensated renal disease will have secondary hypertension before anesthesia (23).
Peripheral volume support is essential 10 to 20 ml/kg/h of crystalloid isotonic fluids given intravenously should be given to maintain adequate circulating volume to the kidney. Ensure adequate analgesia, because pain and sympathetic nervous system stimulation will cause
catecholamine release, vasoconstriction and decreased blood flow to the kidney. Preoperative use of NSAIDs is generally not recommended in patients with renal disease (23).
1.8 Induction, maintenance and monitoring for patients with liver disease
1.8.1 Induction
In general, a minimum dose of induction agent should be used to minimize the negative hemodynamic effect of the agent on hepatic blood flow. Choices concerning induction agents should be made depending on the degree of impairment and the patient’s health status. Thiobarbiturates should be avoided in patients with liver disease. Propofol should be considered a drug of choice for animals with liver disease. Propofol is rapidly redistributed after injection and is helpful in terminating the anesthetic effects (23).
Etomidate, an imidazole anesthetic drug. Etomidate can be used in patients with liver disease because it has excellent cardiovascular support and rapid redistribution (23).
Ketamine is heavily metabolized by the liver in dogs, and prolonged recovery may occur in patients with significant liver disease. A single and small bolus dose is appropriate for patients with mild or moderate liver disease (23).
1.8.2 Maintenance
Halothane should be avoided, but isoflurane or sevoflurane is an appropriate choice for patients with liver disease (23).
1.8.3 Monitoring
Careful attention should be made to maintenance of vital organ blood flow and oxygenation. Blood pressure monitoring and pulse oximetry can be very helpful in this suspect. Mean arterial blood pressure should be maintained above 70 mmHg and oxygen saturation above 95 % in patient with liver disease (23).
1.9 Anesthetic complication
The most common complications during anesthesia are hypotension, hypoventilation, hypoxemia, hypothermia and arrhythmias (bradycardia and tachycardia). The most life-threatening complications are the once in the cardiovascular and respiratory systems (10).
1.9.1 Cardiovascular System Complications 1.9.1.1 Bradycardia
Bradyarrhythmia may lead to severe hypotension, the most common cause of bradycardia during anesthesia is drug-related. α2-agonist increase systemic blood pressure that commonly triggering bradycardia. Opioids (e.g., fentanyl) increase vagal tone and cause bradycardia but with minimal effect of the systemic blood pressure. Bradycardia is addressed if the heart rate is less than 80-100 bpm in cats and small dogs, less than 55-65 bmp in mid-sized dogs, or less than 45-55 bpm in large dogs, especially if arterial blood pressure is in the lower end of the normal range or below
the normal range (48). Treatment of bradyarrhythmia should be considered if the heart rate falls below 60 bmp in large dogs, or 90 bmp in small dogs, especially if the blood pressure monitoring system is not available (49).
In case of bradycardia the anesthesia depth should be decreased, by reducing the concentration of the inhalant agent administered, or give antagonism of α2-agonists with atipamezole, or
administrate anticholinergic. For the treatment of opioid overdose, naloxone can be injected 0.01-0.04 mg/kg IV. If vagal stimulation is suspected as an origin of bradycardia, administer an anticholinergic agent: atropine 0.02-0.04 mg/kg IV (in an emergency), or glycopyrronium 0.005-0.01 mg/kg IV (48).
Anticholinergics tend to be ineffective in patients with a body temperature below 35 C. In such case terbutaline may be considered (0.01 mg/kg IV) (50).
In the case of refractory bradycardia or immediately life-threatening bradycardia, adrenaline 0.01 mg/kg IV might be considered (48).
1.9.1.2 Hypotension
A common complication during anesthesia is hypotension, it can be diagnosed through blood pressure monitoring and evaluation of other physiological parameters (i.e., capillary refill time, peripheral pulse palpation) (10,51). Hypotension is defined as BP values of systolic < 80-90 mmHg, diastolic < 40mmHg and mean < 60-70 mmHg (52).
Hypotension can result in decreased perfusion to vital organs (brain, heart and kidney) and it can lead to dysfunction (53).
Early recognition of hypotension can prevent the negative consequences of inadequate tissue perfusion such as renal, cerebral, and myocardial ischemia. Therefore, routine blood pressure monitoring during anesthesia is important and necessary, especially in a patient that is very old, very young or critically ill and may not have a functional reserve to tolerate inadequate perfusion to vital organs (53).
Many injectable and inhalant anesthetic agent have side effects of decreasing cardiac output (CO), systemic resistance, or both, which can lead to hypotension or low blood pressure. Systemic blood pressure is a product of CO (i.e. stroke volume, heart rate) and systemic vascular resistance. Factors that can affect the development preanesthetic hypotension include; age, underlying disease, duration of anesthesia and number of surgical procedures (53).
Hypotension can be reduced by decreasing the depth of anesthesia and administering crystalloid and/or colloid boluses, and/or administering vasopressors and inotropes (51). If the patients are also bradycardic, then anticholinergic (atropine, glycopyrrolate) or sympathomimetic (ephedrine) can be administered (10).
1.9.1.3 Tachycardia
Tachycardia can be defined as a heart rate higher than 140 bpm in large dogs, 180 bpm in small dogs. The cause of tachycardia during anesthesia is increased sympathetic tone with the release of catecholamines, due to nociception (inadequate analgesia) and/or inadequate depth of anesthesia and in this case, hypertension is generally present (48).
Hypotension due to either hypovolemia or drug-related vasodilation is also a common cause of reflex-tachycardia. Tachycardia during anesthesia can be in case of: hypothermia, endocrine diseases (hyperthyroidism, pheochromocytoma), hypoxemia, hypoventilation or electrolyte imbalance (48).
Tachycardia can be secondary to administration of a drug such as ketamine, alfaxalone, atropine and dopamine (10).
1.9.2 Respiratory System Complications 1.9.2.1 Hypoventilation
An expected effect of general anesthesia is hypoventilation, and can be estimated by observing respiratory rate and depth or quantified by using capnometry. It can be difficult to distinguish a normal from the abnormal tidal volume, normal end-tidal CO2 is approximately 35-40 mmHg in awake
patients and approximately 40-50 mmHg in a patient under light anesthesia. Patient that are under excessive anesthesia depth, has increased CO2 and can be supported by positive pressure ventilation
(51).
1.9.2.2 Hypoxemia
Hypoxemia associated with abnormal pulmonary gas exchange, in small animals intra-operative hypoxemia can occur if there is an underlying pulmonary disease or any acute event occurs during the procedure. In healthy small animal’s hypoxemia is more likely to occur in the postanesthetic period, during extubating when animal losing protected airway, controlled ventilation and enriched inspired oxygen concentration (54).
In animals with healthy lungs that breath in room air should not get hypoxemia in absence of hypoventilation or upper respiratory obstruction. One study of 20 healthy young dogs recovering from anesthesia was documented with a PaO2< 80 mmHg one or more time times after extubating
1.9.3 Thermoregulation complications 1.9.3.1 Hypothermia
Inadvertent perianesthetic hypothermia is one of the most common complications associated with anesthesia in dogs. Hypothermia has been associated with some adverse events, which include pharmacokinetics of anesthetic and analgesic drugs, dysfunction of organ systems, hypotension and delayed recovery (56).
General anesthesia causes thermoregulation impairment characterized by an increase in warm-response thresholds and a decrease in cold-warm-response thresholds (57).
Hypothermia is a decrease in the core body temperature. Body temperatures > 36 C is referred to as mild hypothermia, body temperature > 32 C is referred to moderate hypothermia and body temperature > 30C is associated with sever hypothermia (36).
Decreasing body temperature affects a number of body systems; the sympathetic nervous stimulation produced by hypothermia may lead to bradycardia, cardiac arrhythmias and depression of the baroreceptor reflex (59). The patient temperature should be taken before the administration of premedication and recorded, once premedication has been administered the patient should be kept warm to maintain normothermia. Preoperative warming may be needed if the temperature decreases. Once the patient is anesthetized it should be placed on a heating device and throughout the anesthetic. The temperature should be monitored with an oral probe if possible, and rectal temperature should be taken every 5 minutes and recorded if the equipment is not available for continuous monitoring. The aim is to achieve normothermia throughout the anesthetic (37.8-39.2 C), if the temperature decreases below 37 C during active surface warming additional warming method should be used (60).
1.10 Recovery period
Recovery is a critical phase of anesthesia, which includes continuous patient support, monitoring, and record-keeping. It starts by turning off the anesthetic gas, it does not end at the time of extubating. A patient recovering from anesthesia require monitoring by a trained person who can recognize complications. Although most of the complications occurs throughout the anesthesia, most anesthetic death is associated during the first 3 hours of recovery. 47 percent of canine anesthesia mortalities has been reported to occur during the postoperative period (61).
Once the patient has been extubated, it should be removed from the surgery room into a quiet place. The most important thing is the prevention of hypothermia as it can have serious consequences. Fluid therapy should be continued until the patient is awake enough to drink water unaided especially for patient with kidney disease. Heart and respiratory rate should be monitored until patient is awake. Post-operative analgesics can be necessary (36,42).
2. METHODOLOGY
This research work was carried out in Evidensia Specialistdjursjukhuset (Helsingborg, in Sweden). The collection of data for group two and three started in June 2019 and continued until the end of August 2019, and collection of data for group one was performed in January 2020.
During the data collection, a questionnaire was used for each patient. The questionnaire included animals age, gender, breed, weight, current health condition (healthy, unhealthy), type of premedication, induction, maintenance, IV fluid, and post-surgery medication (1 appendix).
The animal that was enrolled was used in this research based on their health status, and was going under planned surgical procedure (e.g. castration, pyometra, teeth extraction, TPLO, Endoscopy, biopsy of tumors, mammary gland tumor removal).
The patients were divided into 3 groups. Group I (n = 9) consist of patients that were healthy with no significant health problems, and is classified into ASA I, for Group II (n = 9)- of patients with liver diseases (acute or chronic liver failure), and is classified into ASA 2 or 3, and Group III (n = 6)- of patients with kidney diseases (acute or chronic kidney failure), and is classified into ASA 2 or 3. The age, gender, body score and type of surgery was not specifically selected.
The sample consists of 24 dogs from the three different groups. Group I- included 9 healthy dogs (control group), Group II- included 9 dogs with liver diseases, and Group III- included 6 dogs with kidney diseases. All these patients were under general anesthesia and different anesthesia protocols were used based on individualized patient health status.
The physiological parameters that were measured during the surgery when the patient was under general anesthesia were analysed. The different premedication drugs were also analysed to see how they affect the cardiovascular, respiratory and thermoregulation system in patients with kidney and liver diseases. Also, to see which premedication was safest to use and caused fewer side effects for the patients with liver and kidney diseases.
2.1 Patients health status evaluation
All animals that were used in this study were approved by the hospital where the cases were collected. The hospital follows the instructions and the requirements of animal care and keeping. Also, the veterinarians requirements are followed.
Before the animals getting a surgery, they are first undergoing a general consultation there a DVM taking anamnesis and do general examination (HR; RR; CRT; Temp). Further examination was made such as laboratory tests, radiography, ultrasonography, MR, or CT depending on the patient needs.
When the diagnosis was found and cleared out that the patient needed surgery. The patient was moved to the department of surgery. A DVM that is specialist in surgery examine the patient, include HR, RR, CRT. Depending on the health status the DVM placed the patient into an ASA group.
ASA, Physical Status Classification System: 1. Normal healthy patient
2. Patient with mild systemic disease 3. Patient with severe systemic disease
4. Patient with severe systemic disease that is a constant threat to life
5. The moribund patient who is not expected to survive without the operation (8).
All the healthy patient was ASA 1, patient with liver and kidney disease was ASA 2, and some ASA 3.
2.2 General anesthesia
Then an anesthesia protocol was made for the patient, and the protocol is specific for each patient and is considered depending on the health status of the patient and ASA group. All patients during this study were undergoing general anesthesia, which includes premedication, induction, maintenance, and monitoring.
Table 2. Group I (healthy patients) that were investigated in this research No. Species Breed Gender Age
(years)
Weight (kg)
Premedication 1 Dog Phalene Female 5 3,0 Sedator, 0.05ml IM
Semfortan 0.1ml IM 2 Dog Shih tzu Male 4 7,6 Sedator 0.06ml IM
Semfortan 0.25ml IM 3 Dog Shepherd Male 1 30,1 Sedator 0.25ml IM
Semfortan 1.2ml IM Onsior 3.0ml SC 4 Dog Cavalier king Charles spaniel Male 1 6,9 Sedator 0.27ml IM Semfortan 0.05ml IM
5 Dog Mix breed Male 7 31,75 Sedator 0.07ml IM Semfortan 0.5ml IM 6 Dog Rottweiler Male 9 40,5 Sedator 0.35ml IM
Semfortan 1.6ml IM Onsior 4ml SC 7 Dog Labrador retriever Female 4 23,6 Sedator 0.29ml IM Semfortan 0.95ml IM 8 Dog Staffweiler Male 9 16,9 Sedator 0.05ml IV
Semfortan 0.5ml IV 9 Dog Mix breed Male 10 27 Sedator 0.1ml IM
Table 3. Group II (patients with liver diseases) that were investigated in this research
Table 4. Group III (patients with kidney diseases) that were investigated in this research No. Species Breed Gender Age
(years)
Weight (kg)
Premedication 1 Dog Pomeranian Male 8 3,6 Sedator 0.03ml IM
Semfortan 0.1ml IM 2 Dog Mix breed Male 10 6,1 Dexdomitor 0.25 ml IM
Semfortan 0.18 ml IV Prevomax 0.6 ml IV 3 Dog Mix breed Female 12 3,3 Dexdomitor 0,1 ml IM
Semfortan 0,1 ml IM Prevomax 0,33 ml IM 4 Dog Leonberger Male 1 56 Sedator 15 ml IM
Semfortan 0.2 ml IM 5 Dog Retriever Male 1 19,2 Sedator 0.1 ml IM
Butomidor 0.2 ml IM 6 Dog Cocker
spaniel
Female 12 15,9 Sedator 0.04 ml IM Semfortan 0.47 ml IM No. Species Breed Gender Age
(years)
Weight (kg)
Premedication 1 Dog Unknown Female 5 7,9 Semfortan 0.3ml IM 2 Dog Mix breed Female 15 14,0 Semfortan 0.56ml IM 3 Dog Mix breed Male 9 48,5 Semfortan 1.45ml IM
4 Dog Drever Female 3 13,7 Semfortan 1ml IV Stesolid 0.6ml IV 5 Dog German
shepherd
Female 9 45,5 Sedator 0.15 IM
6 Dog Chihuahua Male 3 3,3 Sedator 0.02ml IM Semfortan 0.01ml IM 7 Dog Cavalier king Charles spaniel Female 3 10,3 Sedator 0.04 ml IV Semfortan 0.3ml IV
8 Dog Mix breed Male 9 30 Semfortan 0.6ml IM Midazolam 2ml IV 9 Dog Mix breed Male 9 8,4 Sedator 0.025ml IV
2.2.1 Patients premedication
After deciding the anesthesia protocol, the patient got premedicated. Premedication was decided after the health status of each patient.
Table 5. Premedication used for this research and their doses
2.2.1.1 Patients divided according to their premedications
In each group (Group I, Group II, Group III), the patients were given different premedication, therefore it is subgroups depending on which premedication the patient was given.
In the group 1 (healthy patient), it is two subgroups according to premedication. Subgroup 1- “Sedator 1 mg/ml “ (medetomidine hydrochloride) and “Semfortan 0.1-0.25 mg/kg” (methadone) and subgroup 2- “Sedator 1 mg/ml” (medetomidine hydrochloride), “Semfortan 0.1-0.25 mg/kg” (methadone) and “Onsior 2 mg/kg” (robenacoxib).
In the group 2 (patients with liver diseases), it is five subgroups according to the premedication. Subgroup 1- “Semfortan 0.1-0.25 mg/kg” (methadone), subgroup 2- “Sedator 1 mg/ml” (medetomidine hydrochloride) , subgroup 3 – “Semfortan 0.1-0.25 mg/kg” (methadone) and “Stesolid 0.1-0.25 mg/kg” (diazepam), subgroup 4- “Sedator 1 mg/ml” (medetomidine hydrochloride) and “Midazolam 0.1-0.25 mg/kg” (midazolam), subgroup 5- “Sedator 1 mg/kg”
Brand name Group Active substance Doses for canines
Sedator vet. Alpha2-agonists Medetomidine hydrochloride
1 mg/ml IM
Sedadex Alpha2-agonists Dexmedetomidine hydrochloride
0.5 mg/ml IM
Dexdomitor Alpha2-agonists Dexmedetomidine hydrochloride 0.5 mg/ml IM Midazolam Hameln 5mg/ml Benzodiazepines Midazolam 0.1-0.25 mg/kg IV Stesolid Emulsion 5mg/ml Benzodiazepines Diazepam 0.1-0.25mg/kg IV
Butormidor vet. Opioids Butorphanol 0.1-0.5 mg/kg IM/SC Semfortan vet Opioids Methadone 0.1-0.25 mg/kg IM
Metacam NSAID Meloxicam 1 ml/10kg SC
Onsior Antiinflammatory Robenacoxib 2 mg/kg SC
Bupaq vet. Opioids Buprenorphine 0.01-0.02 mg/kg IM/SC
In group 3 (patients with kidney diseases), it is three subgroups according to the premedication. Subgroup 1- “ Sedator 1 mg/ml” (medetomidine hydrochloride) and “Semfortan 0.1-0.25 mg/kg” (methadone), subgroup 2- “ Dexdomitor 0.5 mg/ml” (dexmedetomidine hydrochloride), “Semfortan 0.1-0.25 mg/kg” (methadone) and “Prevomax 1 ml/10kg” (maropitant), subgroup 3- “Sedator 1 mg/ml” (medetomidine hydrochloride) and “Butomidor 0.1-0.5 mg/kg” (butorphanol).
2.2.2 Induction
When the patient was sedated the patient was placed on the preparation table. Then the patient was prepared for an intravenous catheter. The area was shaved (Andis ADCB Super 2-speed with blade 10 and 40 or Aesculap Exacta (GT416), a tourniquet was placed above the elbow and then the shaved area was cleaned with cotton contained chlorhexidine. Then the intravenous catheter was placed in the cephalic vein, in certain cases. it was placed in the lateral saphenous vein. A 22G intravenous catheter in small dogs, and 20G intravenous catheter in medium and larger sized dogs. NaCl 9 % was flushed into the intravenous catheter to check if it was placed correctly into the vein.
Then induction drug was given to the patient, and when the patient did not show eye reflex or swallowing reflex a tracheal tube was placed into the trachea with help of a laryngoscope if needed.
A bandage was used to prevent the tube to fall out, the bandage was placed around the tube end and then around the ears of the animal or around the mouth depending on the size of the animal. The cuff of the tube was filled with air with help of an empty 10-20 ml syringe.
2.2.3 Maintenance
Oxygen was provided through the anesthesia machine. All patient that were used for this study had a breathing system that was specifically used for the weight. For patients below 10 kg non-rebreathing system where used, and for patients above 10 kg circle non-rebreathing system were used.
When the breathing was frequently, isoflurane was given to make the patient sleep deeper through the surgery. The intravenous fluid was placed onto the intravenous catheter, and was given to the patient throughout the anesthesia.
2.2.4 Monitoring
The monitoring system that was used during this study was Mindray iPM12Vet, and the anesthesia machine with ventilator Mindray WATO EX 20 vet.
An inflatable blood pressure cuff (Maicuff animal blood pressure) was placed around the front leg or the back leg. It measured mechanically the blood pressure such as systolic, diastolic, and MAP. These parameters are written down to the anesthesia protocol every 5 minutes.
A pulse oximeter that is connected to the monitoring system was placed on the tongue, or prepuce, or paw. It measures mechanically the SpO2 and the HR, and these parameters are written
system, and it measures mechanically O2, CO2, and EtCO2. These parameters are written down
to the anesthesia protocol every 15 minutes. A mechanical thermometer from the monitoring system was placed into the esophagus or the anus depending on which type of surgery was performed. This parameter is written down to the anesthesia protocol every 15 minutes. The animal was placed on a heating pad (Pet heat pad) to prevent the animal to lose heat.
A manual examination was also made, to ensure the monitoring system is working correctly. It is important to check HR, RR, Temp, pulse, CRT, and reflexes throughout the anesthesia.
The HR and RR were measured with help of a stethoscope (Littmann Classic III Stethoscope), and the temperature was taken with help of a thermometer (Digital thermometer (GIMA)), and pulse was taken by palpate the saphenous vein.
When the patient was stable, the surgery area was getting prepared and then the patient was unconnected from the monitoring system, intravenous fluid, and the oxygen tube. Then the patient was quickly moved into the surgery room where it was connected to the oxygen tube and isoflurane was turned on and the monitoring system and the intravenous fluid were connected to the patient again. The patient was monitored throughout the whole surgery and all parameters were measured and written down onto the protocol. After the surgery was done, the patient was unconnected from the monitoring system and the isoflurane was turned off and one last manual breath was given to the patient to fresh out the lungs from the isoflurane and the oxygen tube was removed from the tracheal tube. The bandage was removed and the tube was uncuffed with help of a 10-20 ml syringe.
2.2.5 Recovery
The patient was moved into the waking up room and into a separate case and a blanket was placed on top of the patient to prevent hypothermia. The tracheal tube was removed from the patient when eye reflex and swallowing reflex was showed. When the patient was fully woken up it was allowed for the patient to go back home or if it was going stay in the hospital it was moved into the department of patient care.
2.3 Statistical analysis
All statistical analyses were performed using SPSS (IBM SPSS Statistics for Windows, Release 24.0, Chicago, Illinois). The level of significance was set at p <0.05.
Normality was checked using the Shapiro-Wilk test for all variables. One-way Anova was used to compare the physiological variables between the premedications for each group (liver/kidney) separately. Since healthy groups had only two premedication’s Independent T-test was used. Descriptive data are presented as mean SD, mode, and min-max.
