Effect of Daily Prolonged Ketamine Anesthesia on Intraocular Pressure in Monkeys

Abstract

Purpose-To determine if repeated intramuscular ketamine in monkeys on consecutive days affects intraocular pressure (IOP), and if the ketamine-induced IOP change has any relationship to systemic dehydration and/or changes in mean arterial pressure (MAP) of the animals.Methods-Nine monkeys were studied per 4 protocols. IOP was determined hourly for 6-hrs by Goldmann tonometry under ketamine anesthesia on 3 (protocol 1) or 5 (protocols 2 and 3) consecutive days, or on alternating days 1, 3 and 5 (protocol 4). Monkeys in protocols 3 and 4, but not in protocols 1 and 2, received subcutaneous Ringer's fluids at the end of each 6-hr session on days 1-4 or 1, 3 and 5; monkeys in protocols 2 and 3 received intravenous fluid infusion throughout the experiment on day 5. In protocols 2-4, MAP was measured hourly following each IOP measurement.Results-Monkeys receiving ketamine but no Ringer's fluids in protocol 1 or 2 showed significant IOP declines on days 2-3 or 2-4. The IOP declines were greater in magnitude in protocol 1 than in protocol 2. Daily subcutaneous Ringer's fluids appeared to delay IOP declines in protocol 3. Continuous intravenous fluid infusion on day 5 variably prevented IOP declines in protocols 2 and 3. Monkeys receiving ketamine and subcutaneous fluids on alternate days in protocol 4 showed no decline in IOP. No significant relationship between IOP and MAP was observed.Conclusions-Anesthesia induced by repeated intramuscular ketamine on consecutive days may produce significant IOP declines. Systemic dehydration during the anesthesia seems to be the predominant factor contributing to the IOP reduction. However, inter-individual differences in monkeys indicate that multiple factors may be involved. This study also suggests that fluid supplementation plus alternating anesthesia with recovery days may prevent IOP reduction in monkeys resulting from daily-prolonged ketamine anesthesia.

Effect of general anesthetics on IOP in elevated IOP mouse model

“…Because almost all agents for general anesthesia affect the IOP in both humans and animals (Almeida et al, 2004; Artru, 1995; Ausinsch et al, 1975; 1976; 1977; Adams and Barnett, 1966; Badrinath et al, 1986; Bito et al, 1979; Burke and Potter, 1986; Bunch et al, 2008; Camras et al, 2010; Erickson–Lamy et al, 1984; Gelatt et al, 1977; 1982; Hahneberger, 1976; Hahnenberger 1976a; 1976b; Hayreh et al, 1991; Hofmeister et al, 2006; 2008; Jia et al, 2000; Johnson et al, 2008; Komaromy et al, 1998; Krupin et al, 1980; Mirakhur et al, 1990; Mowafi et al, 2003; Murphy, 1985; Nagdeve et al, 2006; Sator-Katzenschlager et al, 2002; Schäfer et al, 2002; Schnell et al, 1996) and the repetitive use of anesthetics might cause either neuronal degeneration (Istaphanous and Loepke, 2009; Mellon et al, 2007) or neuroprotection (Hudetz and Pagel, 2010; Koerner and Brambrink, 2006; Mortier et al, 2000) in glaucomatous retina, measuring IOP from conscious animals would avoid the un-wanted effects of anesthetics on the IOP measurement and potential anesthesia-induced confounding of experimental results. Towards this end, measuring conscious IOP in rats after behavioral training seems to provide a reliable measurement of IOP.…”

“…Numerous reports have shown that various anesthetics could alter IOP in humans (Ausinsch et al, 1975; 1976; 1977; Adams and Barnett, 1966; Badrinath et al, 1986; Mirakhur et al, 1990; Mowafi et al, 2003; Murphy, 1985; Nagdeve et al, 2006; Sator-Katzenschlager et al, 2002; Schäfer et al, 2002), monkeys (Bito et al, 1979; Burke and Potter, 1986; Bunch et al, 2008; Erickson–Lamy et al, 1984; Hahneberger, 1976; Hahnenberger 1976a; Hayreh et al, 1991; Komaromy et al, 1998; Krupin et al, 1980), dogs (Almeida et al, 2004; Artru, 1995; Gelatt et al, 1977; 1982; Hofmeister et al, 2006; 2008), cats (Burke and Potter, 1986; Hahnenberger, 1976b), rabbits (Burke and Potter, 1986; Schnell et al, 1996), rats (Jia et al, 2000), and mice (Camras et al, 2010; Jia et al, 2000; Johnson et al, 2008). Most of the anesthetics have been reported to decrease IOP in human and other animals.…”

“…Some reports showed that ketamine decreases IOP in human (Ausinsch et al, 1976; Blumberg et al, 2007), monkeys (Bunch et al, 2008; Hahnenberger, 1976a), rats (Jia et al, 2000), and mice (Jia et al, 2000; Johnson et al, 2008). Others show that ketamine increases IOP in human (Bar-Ilan and Pessah, 1986; Corssen and Hoy, 1967; Nagdeve et al, 2006; Yoshikawa and Murai, 1971), dogs (Hofmeister et al, 2006), cats (Hahnenberger, 1976b), and rabbits (Ghaffari and Moghaddassi, 2010; Schutten and Van Horn, 1977).…”

Study Design and Methodologies for Evaluation of Anti-glaucoma Drugs

“…The Cynomolgus (also known as the crabeating macaque, Macaca fascicularis) and Rhesus macaque (Macaca mulatta) are the most widely used and best studied. Their close phylogeny and high homology with humans makes them excellent test species and their responsiveness to [69][70][71][72][73][74][75][76][77][78]. Important differences between macaques and humans do exist, however, including a smaller corneal surface area and overall body mass which may affect the pharmacokinetics, ADME, and systemic toxicity of topically applied anti-glaucoma drugs.…”

Contenção farmacológica em primatas não-humanos com emprego de ketamina e xilazina. Uma revisão bibliográfica

“…Os animais permanecem com olhos abertos, apresentando bom tônus nos músculos mandibulares, com reflexos laringeais e faringeais ativos, enquanto que a analgesia aparenta ser extremamente boa (HALL e CLARCK, 2001;BUNCH et al, 2008).…”