Effects of diazepam, ketamine, and their combination on intraocular pressure in normal dogs

Ketamine has been implicated as causing increases in intraocular pressure. The purpose of this study is to document the effects of ketamine, diazepam, and their combination on intraocular pressure (IOP) in normal, unpremedicated dogs. Random-source dogs were assigned to one of five groups of 10 dogs each: ketamine 5 mg kg^–1 (KET5), ketamine 10 mg kg^–1 (KET10), diazepam 0.5 mg kg^–1 (VAL), ketamine 10 mg kg^–1 with diazepam 0.5 mg kg^–1 (KETVAL), saline 0.1 mL kg^–1 (SAL), all given intravenously. A baseline IOP was measured before injection, immediately after injection, and at 5, 10, 15, and 20 minutes following injection. IOP was increased over baseline immediately after injection in the KET5, KET10, and KETVAL groups; at 5, 10, and 15 minutes in the KET5 group; and at 20 minutes in the KETVAL group. The mean IOP change compared to SAL increased immediately after injection and at 5 minutes in the KET5, KET10, and KETVAL groups; at 10 and 15 minutes in the KET5 group, and at 20 minutes in the KETVAL group. The mean IOP increased up to 5.7, 3.2, and 3.1 mm Hg over mean baseline in the KET5, KET10, and KETVAL groups, respectively. All dogs in the KET5 group and the majority in the KETVAL and KET10 groups had an increase in their IOP over baseline. Ketamine caused a clinically and statistically significant elevation in IOP over baseline and compared to SAL. The concurrent addition of diazepam did not blunt this increase. Ketamine should be avoided in dogs with corneal trauma, glaucoma, or in those undergoing intraocular surgery.     

Effects of the topically applied calcium-channel blocker flunarizine on intraocular pressure in clinically normal dogs

OBJECTIVE: To determine effects of the topically applied calcium-channel blocker flunarizine on intraocular pressure (IOP) in clinically normal dogs. ANIMALS: 20 dogs. PROCEDURES: Baseline diurnal IOPs were determined by use of a rebound tonometer on 2 consecutive days. Subsequently, 1 randomly chosen eye of each dog was treated topically twice daily for 5 days with 0.5% flunarizine. During this treatment period, diurnal IOPs were measured. In addition, pupillary diameter and mean arterial blood pressure (MAP) were evaluated. Serum flunarizine concentrations were measured on treatment day 5. Intraday fluctuation of IOP was analyzed by use of an ANOVA for repeated measures and a trend test. Changes in IOP from baseline values were assessed and compared with IOPs for the days of treatment. Values were also compared between treated and untreated eyes. RESULTS: A significant intraday fluctuation in baseline IOP was detected, which was highest in the morning (mean +/- SE, 15.8 +/- 0.63 mm Hg) and lowest at night (12.9 +/- 0.61 mm Hg). After 2 days of treatment, there was a significant decrease in IOP from baseline values in treated (0.93 +/- 0.35 mm Hg) and untreated (0.95 +/- 0.34 mm Hg) eyes. There was no significant treatment effect on pupillary diameter or MAP. Flunarizine was detected in serum samples of all dogs (mean +/- SD, 3.89 +/- 6.36 microg/L). CONCLUSIONS AND CLINICAL RELEVANCE: Topically applied flunarizine decreased IOP in dogs after 2 days of twice-daily application. This calcium-channel blocker could be effective in the treatment of dogs with glaucoma.     

Propofol versus thiopental: effects on peri-induction intraocular pressures in normal dogs

ObjectiveTo determine the effects of propofol or thiopental induction on intraocular pressures (IOP) in normal dogs.Study designProspective randomized experimental study.AnimalsTwenty-two random-source dogs weighing 19.5 ± 5.3 kg.MethodsDogs were randomly assigned to receive propofol 8 mg kg⁻¹ IV (group P) or thiopental 18 mg kg⁻¹ IV (group T) until loss of jaw tone. Direct arterial blood pressure, arterial blood gasses, and IOP were measured at baseline, after pre-oxygenation but before induction, before endotracheal intubation, and after intubation.ResultsThere were no significant differences between groups with regard to weight, body condition score, breed group, or baseline or before-induction IOP, arterial blood pressure, or blood gases. The baseline IOP was 12.9 mmHg. Before endotracheal intubation, IOP was significantly higher compared to baseline and before induction in dogs receiving propofol. After intubation with propofol, IOP was significantly higher compared to thiopental and was significantly higher compared to before induction. After intubation, IOP was significantly lower compared to before intubation in dogs receiving thiopental. Propofol increased IOP before intubation by 26% over the before-induction score and thiopental increased IOP by 6% at the same interval. The IOP in group P remained 24% over the before induction score whereas thiopental ultimately decreased IOP 9% below baseline after intubation. There was no significant relationship between any cardiovascular or blood gas parameter and IOP at any time. There was no significant relationship between the changes in any cardiovascular or blood gas parameter and the changes in IOP between time points.Conclusions and clinical relevancePropofol caused a significant increase in IOP compared to baseline and thiopental. Thiopental caused an insignificant increase in IOP which decreased after intubation. Propofol should be avoided when possible in induction of anesthesia in animals where a moderate increase in IOP could be harmful.     

Influence of lidocaine and diazepam on peri-induction intraocular pressures in dogs anesthetized with propofol–atracurium

The purpose of this study was to evaluate the effects on the intraocular pressure (IOP) of lidocaine or diazepam administered intravenously (IV) before induction of anesthesia with propofol-atracurium and orotracheal intubation in normal dogs, as well as the effects on the IOP of lidocaine applied topically to the larynx after induction with propofol-atracurium. We randomly assigned 32 random-source dogs, obtained from municipal pounds, to receive the following: lidocaine, 2 mg/kg IV, with saline, 0.1 mL/kg topically applied to the larynx (LIDOsal); saline, 0.1 mL/kg IV, with lidocaine, 2 mg/kg topically applied to the larynx (SALlido); diazepam (Valium), 0.25 mg/kg IV, with saline, 0.1 mL/kg topically applied to the larynx (VALsal); or saline, 0.1 mL/kg IV, with saline, 0.1 mL/kg topically applied to the larynx (SALsal). We measured arterial pressure directly, by means of an indwelling catheter placed in a peripheral artery. Anesthesia was induced with propofol, 8 mg/kg IV, until loss of jaw tone, followed by atracurium, 0.3 mg/kg IV. We measured the IOP in triplicate in each eye before premedication, before induction, before intubation, and after intubation. After induction, the IOP was significantly increased except in the VALsal group, in which the IOP was significantly lower than in the negative-control group before intubation. After intubation, the IOP was significantly elevated in all the groups compared with the values before induction. Cardiovascular parameters were essentially similar in all the groups, except for a significant increase in blood pressure after intubation in the SALlido group. Thus, propofol-atracurium anesthesia causes an increase in IOP that is blunted by diazepam. However, diazepam does not blunt the increase in IOP observed with intubation.     

Effects of graded doses of propofol for anesthesia induction on cardiovascular parameters and intraocular pressures in normal dogs

ObjectiveTo determine the effects of graded doses of propofol on cardiovascular parameters and intraocular pressures (IOP) in normal dogs.Study designProspective, randomized, modified Latin square, cross-over experimental study.AnimalsEleven adult random-source dogs weighing 20.2 ± 5.7 kg.MethodsThere were three treatment groups: propofol 8 mg kg^?1 intravenous (IV) until loss of jaw tone (Group P), propofol until loss of jaw tone +20% (Group P20), and propofol until loss of jaw tone +50% (Group P50). Atracurium 0.1 mg kg^?1 IV was administered in all treatments immediately after the propofol. All dogs received the three treatments in a randomized order, with at least a one week interval between treatments. Direct arterial blood pressure and IOP by applanation tonometry were obtained at baseline, after 5 minutes of pre-oxygenation (before induction), before, and after intubation. Blood gas samples were obtained at baseline, after pre-oxygenation, and before intubation.ResultsThere was no significant difference in IOP readings at any time point among groups. The IOP was significantly higher before intubation versus before induction in all three groups. There was a significantly smaller change in systolic, mean (MAP), and diastolic (DAP) arterial pressures in the P50 group compared with the P group after intubation. There was a significantly smaller change in MAP and DAP in the P50 group compared with the P20 group after intubation. The increase in CO₂ from before induction to before intubation was significantly greater in the P50 group than in the P or P20 groups.Conclusions and clinical relevanceGraded doses of propofol did not affect the increase in IOP observed with propofol induction in normal dogs. Higher doses of propofol are of no apparent additional benefit in animals who cannot tolerate an abrupt increase in IOP but may be of benefit in dogs who cannot tolerate an abrupt increase in blood pressure accompanying orotracheal intubation.     

Effects of oral administration of methazolamide on intraocular pressure and aqueous humor flow rate in clinically normal dogs

OBJECTIVE: To determine magnitude and duration of the effect of oral administration of methazolamide at 2 dosages on intraocular pressure (IOP) in dogs in single-dose and multiple-dose trials and to determine aqueous humor flow rate (AHFR) by use of anterior segment fluorophotometry before and during treatment. ANIMALS: 25 healthy adult Beagles. PROCEDURE: Baseline IOPs and AHFRs were determined on days 0 and 1, respectively. On day 2, the single-dose trial was initiated with oral administration of 25 or 50 mg of methazolamide at 7 AM to 2 groups of 10 dogs each. Five dogs served as controls. In the multiple-dose trial, the same dogs received 25 or 50 mg of methazolamide at 7 AM and at 3 and 11 PM on days 3 through 9. RESULTS: Intraocular pressures varied diurnally with highest IOPs in the morning. In the single-dose trial, IOP decreased significantly at 3 to 6 hours after treatment and then increased significantly at later time points, compared with baseline values. In the multiple-dose trial, dogs in both treatment groups had significantly lower IOPs during the treatment period at 10 AM and 1 PM but not at 6 and 9 PM, compared with baseline values. In both treatment groups morning IOPs had returned to baseline values by the first day after treatment. Evening IOPs were significantly increased by 2 to 3 days after treatment, compared with baseline values. The AHFRs in both treatment groups were significantly lower than pretreatment AHFRs. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of methazolamide decreases IOPs and AHFRs in clinically normal dogs, with effectiveness diminishing in the evening.     

The effects of ketamine‐midazolam anesthesia on intraocular pressure in clinically normal dogs

Objective To determine the effects of intravenous ketamine‐midazolam anesthesia on intraocular pressure (IOP) in ocular normotensive dogs. Animals Thirteen adult mixed‐breed dogs. Procedures Dogs were randomly assigned to treatment (n = 7) and control (n = 6) groups. Dogs in the treatment group received intravenous ketamine 15 mg/kg and midazolam 0.2 mg/kg and dogs in the control group received intravenous saline. The time of intravenous drug injection was recorded (T₀). Measurements of IOP were then repeated 5 min (T₅) and 20 min (T₂₀) following the intravenous administration of ketamine‐midazolam combination and saline in both groups. Results Measurements showed normal IOP values in both groups. The mean ± SD baseline IOP values for treatment and control groups were 13.00 ± 1.47 and 10.33 ± 2.20, respectively. For baseline IOP values, there was no significant difference between treatment and control groups (P = 0.162). In the treatment group, the subsequent post‐treatment mean ± SD values were 15.64 ± 2.17 (5 min), and 14.92 ± 1.98 (20 min). There was no evidence of statistical difference between baseline values and post‐treatment values after treatment with ketamine‐midazolam (P₅ = 0.139; P₂₀ = 0.442). In control eyes, the mean ± SD values at 5 and 20 min were 10.41 ± 2.01 and 10.16 ± 1.69, respectively. There was no significant difference between baseline values and post‐treatment values in control group (P₅ = 1.000; P₂₀ = 1.000). Conclusion Ketamine‐midazolam combination has no clinically significant effect on IOP in the dog.     

Isoamylases in clinically normal dogs

Isoenzymes of canine serum amylase were evaluated by electrophoresis on cellulose acetate membranes in a discontinuous buffer system. Two isoamylase groups were identified in the serum of clinically normal dogs. Most of the serum amylase activity was the more cathodal isoamylase. The anodal isoamylase was rarely observed in serum from normal dogs and, when present, accounted for little of the enzymatic activity. Amylase activities of various tissues were determined and isoenzymes were identified. The anodal isoenzyme was found in the pancreas and uterus. The cathodal isoamylase had its origin mainly from the intestinal tract. Activities of other tissues were not greater than was serum amylase activity. Effects of feeding upon total serum amylase activity and isoenzyme composition also were examined over a period of 5 minutes to 7 hours. Feeding did not markedly alter the serum amylase activity.     

Stress leak point pressures and urethral pressure profile tests in clinically normal female dogs.

OBJECTIVE: To develop a stress leak point pressure (LPP) test for dogs, determine LPP for continent female dogs, and determine urethral pressure profile (UPP) values for nonanesthetized, continent female dogs. ANIMALS: 22 continent female dogs weighing from 21 to 29 kg. PROCEDURE: A standard UPP test and a modification of the LPP test used in women were performed on all dogs. On 3 occasions, dogs underwent UPP testing while awake. They then were anesthetized with propofol, and LPP was measured at bladder volumes of 75, 100, and 150 ml. For LPP tests, abdominal pressure was applied by inflating a human blood pressure cuff placed around the dog's abdomen. LPP were recorded through a urethral catheter (bladder LPP) and a rectal balloon catheter (abdominal LPP). RESULTS: Mean +/- SD and median maximal urethral closure pressure was 110.1+/-20.2 and 109.0 cm water, respectively. Mean bladder LPP for the 75, 100, and 150 ml bladder volumes was 172.4 cm water. Significant differences among LPP for the 3 bladder volumes were not detected. CONCLUSIONS: Stress LPP can be recorded in female dogs.     

Diseased dogs isoamylases in clinically normal and diseased dogs

Isoamylases in normal canine sera were separated on cellulose acetate membranes using a discontinuous buffer system without EDTA. Four peaks of amylase activity were present in 17 of 24 sera. Normal values were established. The majority of activity was present in Peak 4 (cathodal isoamylase). Tissue extracts of pancreas, duodenum, kidney, lung, testis, spleen and uterus-ovaries contained Peak 4 isoamylase. Liver and salivary gland lacked all isoamylase activity. Pancreas contained Peak 3 in addition to Peak 4 isoamylase. A tissue origin for Peaks 1 and 2 was not identified. An overall lack of resolution resulted from the inclusion of EDTA in the electrophoresis buffer system. This may account for previous findings suggesting that pancreatic amylase is not present in normal canine serum. An increase in the Peak 3 isoamylase was present in dogs with pancreatitis while dogs with pancreatic atrophy had a decrease in all isoamylases. Total amylase activity was significantly (p < 0.05) decreased in dogs with pancreatic atrophy.     

Effects of intravenous lidocaine, ketamine, and the combination on the minimum alveolar concentration of sevoflurane in dogs

ObjectiveTo evaluate the effects of intravenous lidocaine (L) and ketamine (K) alone and their combination (LK) on the minimum alveolar concentration (MAC) of sevoflurane (SEVO) in dogs.Study designProspective randomized, Latin-square experimental study.AnimalsSix, healthy, adult Beagles, 2 males, 4 females, weighing 7.8 – 12.8 kg.MethodsAnesthesia was induced with SEVO in oxygen delivered by face mask. The tracheas were intubated and the lungs ventilated to maintain normocapnia. Baseline minimum alveolar concentration of SEVO (MAC_B) was determined in duplicate for each dog using an electrical stimulus and then the treatment was initiated. Each dog received each of the following treatments, intravenously as a loading dose (LD) followed by a constant rate infusion (CRI): lidocaine (LD 2 mg kg⁻¹, CRI 50 μg kg⁻¹minute⁻¹), lidocaine (LD 2 mg kg⁻¹, CRI 100 μgkg⁻¹ minute⁻¹), lidocaine (LD 2 mg kg⁻¹, CRI 200 μg kg⁻¹ minute⁻¹), ketamine (LD 3 mg kg⁻¹, CRI 50 μg kg⁻¹ minute⁻¹), ketamine (LD 3 mgkg⁻¹, CRI 100 μg kg⁻¹ minute⁻¹), or lidocaine (LD 2 mg kg⁻¹, CRI 100 μg kg⁻¹ minute⁻¹) + ketamine (LD 3 mg kg⁻¹, CRI 100 μg kg⁻¹ minute⁻¹) in combination. Post-treatment MAC (MAC_T) determination started 30 minutes after initiation of treatment.ResultsLeast squares mean ± SEM MAC_B of all groups was 1.9 ± 0.2%. Lidocaine infusions of 50, 100, and 200 μg kg⁻¹ minute⁻¹ significantly reduced MAC_B by 22.6%, 29.0%, and 39.6%, respectively. Ketamine infusions of 50 and 100 μg kg⁻¹ minute⁻¹ significantly reduced MAC_B by 40.0% and 44.7%, respectively. The combination of K and L significantly reduced MAC_B by 62.8%.Conclusions and clinical relevanceLidocaine and K, alone and in combination, decrease SEVO MAC in dogs. Their use, at the doses studied, provides a clinically important reduction in the concentration of SEVO during anesthesia in dogs.     

Cardiopulmonary effects of anesthetic induction with thiopental, propofol, or a combination of ketamine hydrochloride and diazepam in dogs sedated with a combination of medetomidine and hydromorphone

OBJECTIVE: To evaluate the cardiopulmonary effects of anesthetic induction with thiopental, propofol, or ketamine hydrochloride and diazepam in dogs sedated with medetomidine and hydromorphone. ANIMALS: 6 healthy adult dogs. PROCEDURES: Dogs received 3 induction regimens in a randomized crossover study. Twenty minutes after sedation with medetomidine (10 microg/kg, IV) and hydromorphone (0.05 mg/kg, IV), anesthesia was induced with ketamine-diazepam, propofol, or thiopental and then maintained with isoflurane in oxygen. Measurements were obtained prior to sedation (baseline), 10 minutes after administration of preanesthetic medications, after induction before receiving oxygen, and after the start of isoflurane-oxygen administration. RESULTS: Doses required for induction were 1.25 mg of ketamine/kg with 0.0625 mg of diazepam/kg, 1 mg of propofol/kg, and 2.5 mg of thiopental/kg. After administration of preanesthetic medications, heart rate (HR), cardiac index, and PaO(2) values were significantly lower and mean arterial blood pressure, central venous pressure, and PaCO(2) values were significantly higher than baseline values for all regimens. After induction of anesthesia, compared with postsedation values, HR was greater for ketamine-diazepam and thiopental regimens, whereas PaCO(2) tension was greater and stroke index values were lower for all regimens. After induction, PaO(2) values were significantly lower and HR and cardiac index values significantly higher for the ketamine-diazepam regimen, compared with values for the propofol and thiopental regimens. CONCLUSIONS AND CLINICAL RELEVANCE: Medetomidine and hydromorphone caused dramatic hemodynamic alterations, and at the doses used, the 3 induction regimens did not induce important additional cardiovascular alterations. However, administration of supplemental oxygen is recommended.     

Ureterocolonic anastomosis in clinically normal dogs

Ureterocolonic anastomosis was evaluated in 13 clinically normal dogs. Urinary continence was maintained after surgery, and the procedure was completed without technique errors in all but 2 dogs. Three dogs died within 5 weeks (2 of undetermined causes and 1 of aspiration pneumonia and neurologic disease), and 1 dog was euthanatized 4 months after surgery because of neurologic signs. Two healthy dogs were euthanatized 3 months after surgery for light microscopic evaluation of their kidneys. Five dogs were euthanatized 6 months after surgery for light microscopic evaluation of their kidneys. Gastrointestinal and neurologic disturbances developed in 4 dogs at various postoperative intervals. Plasma ammonia concentration measured in 2 dogs with neurologic signs was increased. Plasma ammonia concentration measured in 5 dogs without neurologic signs was within normal limits. All 5 dogs, in which metabolic acidosis was diagnosed, had high normal or above normal serum chloride concentration. Serum urea nitrogen values were increased after surgery because of colonic absorption of urea. Serum creatinine concentration was increased in 1 dog 6 months after surgery. Individual kidney glomerular filtration rate was reduced in 38% (3/8) of the kidneys from 4 other dogs at 6 months after surgery. Of 5 dogs euthanatized at 3 to 4 months after surgery, 4 had bilateral pyelitis, and 1 had unilateral pyelonephritis. Six months after surgery, pyelonephritis was diagnosed in 40% (4/10) of the kidneys from 5 dogs. The ureterocolonic anastomosis procedure is a salvage procedure that should allow complete cystectomy. However, variable degrees of metabolic acidosis, hyperammonemia, and neurologic disease may result.     

Use of ketamine, xylazine, and diazepam anesthesia with retrobulbar block for phacoemulsification in dogs

Objective  The study was undertaken to evaluate the use of ketamine, xylazine, and diazepam along with a local retrobulbar nerve block for routine phacoemulsification in the dog.
Animals  Ten clinically healthy mixed-breed dogs of either sex, weighing between 10 and 15 kg.
Procedures  Ten mixed-breed dogs were selected for unilateral cataract removal by phacoemulsification. Standard preoperative preparations for cataract surgery were followed. Pre-anesthetic medication consisted of atropine sulfate (0.02 mg/kg, SC). Anesthesia was induced by xylazine HCl (1.0 mg/kg, IM) followed by ketamine (5.0 mg/kg, IM). Anesthesia was maintained subsequently with IV ketamine and diazepam to effect and depth of anesthesia was assessed clinically by pedal reflex and jaw reflex. After induction of anesthesia, a retrobulbar nerve block was performed using 2 mL of 2% lignocaine. Eye position was graded after retrobulbar block and IOP was examined preoperative, post-anesthetic, 6 h postoperative and 24 h after surgery. Phacoemulsification was performed using the phaco-chop technique and an intraocular lens was placed. Anesthetic recovery and postoperative recovery following surgery was recorded.
Result  The exposure of the globe in all the dogs was adequate; the desired central fixation of the eye was obtained and surgery could be performed uneventfully. The mean IOP recorded after induction of anesthesia was 15.75 ± 0.82, which was not significantly ( P  > 0.01) different from pre-anesthetic values (14.85 ± 0.85).
Conclusion  Phacoemulsification was successfully performed with this anesthetic regimen without encountering major intraoperative or anesthetic complications.     

Effects of chlorothiazide on urinary excretion of calcium in clinically normal dogs.

Administration of thiazide diuretics has been recommended to prevent calcium oxalate urolith development in dogs. To evaluate the effects of thiazide diuretics in dogs, 24-hour urine excretion of calcium was measured in 6 clinically normal Beagles after administration of chlorothiazide (CTZ) for 2 weeks, administration of CTZ for 10 weeks, and administration of calcium carbonate and CTZ for 2 weeks. Compared with baseline values, 24-hour urine calcium excretion did not decrease after CTZ administration. When CTZ was given at a high dosage (130 mg/kg of body weight), urinary calcium excretion was significantly (P < 0.04) higher than baseline values. Based on these observations, we do not recommend CTZ for treatment or prevention of canine calcium oxalate urolithiasis.     

Effects of topical application of a 2% solution of dorzolamide on intraocular pressure and aqueous humor flow rate in clinically normal dogs

OBJECTIVE: To evaluate effects of topical application of a 2% solution of dorzolamide on intraocular pressure (IOP) and aqueous humor flow rate in clinically normal dogs. ANIMALS: 15 Beagles. PROCEDURE: The IOP was measured in both eyes of all dogs for 3 days to determine baseline values. In a single-dose study, 50 microl of dorzolamide or control solution was applied in both eyes at 7:00 AM, and IOP was measured 7 times/d. In a multiple-dose study, dorzolamide or control solution was applied to both eyes 3 times/d for 6 days, and IOP was measured 4 times/d during treatment and for 5 days after cessation of treatment. Aqueous humor flow rate was measured for all dogs fluorophotometrically prior to treatment and during the multiple-dose study. RESULTS: In the single-dose study, dorzolamide significantly decreased IOP from 30 minutes to 6 hours after treatment. Mean decrease in IOP during this time span was 3.1 mm Hg (18.2%). Maximal decrease was detected 6 hours after treatment (3.8 mm Hg, 22.5%). In the multiple-dose study, dorzolamide decreased IOP at all time points, and maximal decrease was detected 3 hours after treatment (4.1 mm Hg, 24.3%). Mean aqueous humor flow rate decreased from 5.9 to 3.4 microl/min (43%) after treatment in the dorzolamide group. CONCLUSIONS AND CLINICAL RELEVANCE: Topical application of a 2% solution of dorzolamide significantly decreases IOP and aqueous humor flow rate in clinically normal dogs. Therefore, topical administration of dorzolamide should be considered for the medical management of dogs with glaucoma.