Median effective dose (ED50) of paracetamol and morphine for postoperative pain: a study of interaction.

BACKGROUND: Paracetamol is widely used to treat postoperative pain and is well known for its morphine-sparing effect. Therefore, the effect of morphine-paracetamol combination can be synergistic, additive, or infra-additive. The primary aim of our study is to define the median effective analgesic doses (ED50s) of paracetamol, morphine, and the combination of both. Also, the nature of the interaction for postoperative pain after moderately painful surgery using an up-and-down method and isobolographic analysis was determined. METHODS: Ninety patients, undergoing moderately painful surgery, were included in one of the three groups. Determination of the median ED50s was performed by the Dixon and Mood up-and-down method. Initial doses were 1.5 g and 5 mg, with dose adjustment intervals of 0.5 g and 1 mg, in the paracetamol and morphine groups, respectively. The initial doses of paracetamol and morphine were 1.5 g and 3 mg, in the paracetamol-morphine combination group with dose adjustment intervals of 0.25 g for paracetamol and 0.5 mg for morphine. Analgesic efficacy was defined as a reduction to or <3 on a 0-10 numeric rating scale, 45 min after the beginning of drug administration. Isobolographic analysis was used to define the nature of their interaction. RESULTS: The median ED50s of paracetamol and morphine were 2.1 g and 5 mg, respectively. The median ED50 of the combination was 1.3 g for paracetamol and 2.7 mg for morphine. CONCLUSIONS: Our study showed that the combination of the paracetamol and morphine produces an additive analgesic effect. Clinical trial registration NCT01366313.

A systematic review and meta-analysis of the i-gel(®) vs laryngeal mask airway in adults.

We systematically reviewed 31 adult randomised clinical trials of the i-gel(®) vs laryngeal mask airway. The mean (95% CI) leak pressure difference and relative risk (95% CI) of insertion on the first attempt were similar: 0.40 (-1.23 to 2.02) cmH2 O and 0.98 (0.95-1.01), respectively. The mean (95% CI) insertion time and the relative risk (95% CI) of sore throat were less with the i-gel: by 1.46 (0.33-2.60) s, p = 0.01, and 0.59 (0.38-0.90), p = 0.02, respectively. The relative risk of poor fibreoptic view through the i-gel was 0.29 (0.16-0.54), p < 0.0001. All outcomes displayed substantial heterogeneity, I(2)  ≥ 75%. Subgroup analyses did not decrease heterogeneity, but suggested that insertion of the i-gel was faster than for first-generation laryngeal mask airways and that the i-gel leak pressure was higher than first generation, but lower than second-generation, laryngeal mask airways. A less frequent sore throat was the main clinical advantage of the i-gel.

Minimal alveolar concentration of sevoflurane for maintaining bispectral index below 50 in morbidly obese patients.

BACKGROUND: Morbid obesity is associated with important differences in pharmacokinetics and pharmacodynamics. The aim of this study was to determine minimum alveolar concentration of sevoflurane for maintaining bispectral index (BIS) below 50 (MACBIS50 ) in morbidly obese patients undergoing bariatric surgery using the Continual Reassessment Method (CRM) method. METHODS: Twenty-four morbidly obese patients (body mass index 40-70 kg/m(2) ) were enrolled in our study. Twenty minutes following pre-medication with fentanyl 100 µg, general anaesthesia was induced using propofol 2 mg/kg and cisatracurium 2 mg/kg to facilitate tracheal intubation. The lowest BIS score was recorded following induction. Thereafter, when BIS began to increase > 60, maintenance of anaesthesia was started with a pre-determined end-tidal sevoflurane concentration (ET Sevo) and maintained for 10 min followed by 1-min assessment of BIS taken at 10-s intervals to determine the ET Sevo. The ET Sevo leading to a probability close to 80% success was calculated using the CRM, and the MACBIS50 leading to 50% success was calculated by fitting the data to a dose-probability sigmoid curve, respectively. RESULTS: The ET Sevo able to maintain BIS value below 50 was 1.8% in 67% [95% confidence interval (CI) 0.44-0.86] and higher in the remaining 33% of the patients and the ET Sevo leading to a BIS value below 50 in 50% of the patients (MACBIS50 ) was 1.6 ± 0.10%. CONCLUSIONS: The calculated values (1.8% and 1.6%) were higher than that previously reported in normal adult patients (0.97%; 95% CI 0.89-1.1%) and less than that reported in children (2.8%; 95% CI 2.7-3.1%).

Postoperative intravenous morphine titration.

Relief of acute pain during the immediate postoperative period is an important task for anaesthetists. Morphine is widely used to control moderate-to-severe postoperative pain and the use of small i.v. boluses of morphine in the post-anaesthesia care unit allows a rapid titration of the dose needed for adequate pain relief. The essential principle of a titration regimen must be to adapt the morphine dose to the pain level. Although morphine would not appear to be the most appropriate choice for achieving rapid pain relief, this is the sole opioid assessed in many studies of immediate postoperative pain management using titration. More than 90% of the patients have pain relief using a protocol of morphine titration and the mean dose required to obtain pain relief is 12 (7) mg, after a median of four boluses. Sedation is frequent during i.v. morphine titration and should be considered as a morphine-related adverse event and not evidence of pain relief. The incidence of ventilatory depression is very low when the criteria to limit the dose of i.v. morphine are enforced. Morphine titration can be used with caution in elderly patients, in children, or in obese patients. In practice, i.v. morphine titration allows the physician to meet the needs of individual patients rapidly and limits the risk of overdose making this method the first step in postoperative pain management.

Ondansetron does not block paracetamol-induced analgesia in a mouse model of fracture pain.

BACKGROUND: The aim of this study was to assess any interaction between ondansetron and paracetamol on a model of post-fracture pain in mice. METHODS: In protocol A, after fracture of the tibia, mice were assigned to four groups: paracetamol 30 mg kg⁻¹, paracetamol 50 mg kg⁻¹, paracetamol 100 mg kg⁻¹, or a saline vehicle i.p. In protocol B, after fracture of the tibia, mice were randomized to receive either paracetamol (100 mg kg⁻¹) plus saline (vehicle), paracetamol (100 mg kg⁻¹) plus ondansetron (1 mg kg⁻¹), paracetamol (100 mg kg⁻¹) plus ondansetron (2 mg kg⁻¹), saline plus ondansetron (2 mg kg⁻¹), or saline plus saline i.p. Three tests were used to assess pain behaviour: von Frey filament application, hot-plate test, and a subjective pain scale. Rescue analgesia with morphine was administered as necessary. RESULTS: In protocol A, paracetamol (100 mg kg⁻¹)-treated animals had less mechanical nociception, thermal nociception, and a lower subjective pain scale rating, when compared with those receiving paracetamol at 30 or 50 mg kg⁻¹ or saline [ED50 paracetamol=46.3 (6.34) mg kg⁻¹]. No difference was found between paracetamol (30 mg kg⁻¹) and saline-treated animals. In protocol B, the mechanical withdrawal threshold, the thermal withdrawal latency, and the subjective pain scale were lower after injection of paracetamol (100 mg kg⁻¹)+saline, paracetamol (100 mg kg⁻¹)+ondansetron (1 mg kg⁻¹), and paracetamol (100 mg kg⁻¹)+ondansetron (2 mg kg⁻¹), whereas in mice receiving saline+ondansetron (2 mg kg⁻¹) or saline+saline, there was no difference. CONCLUSION: We found that paracetamol 100 mg kg⁻¹ blocked the development of hyperalgesia and allodynia after fracture pain and ondansetron did not modify the antinociceptive effect of paracetamol in this model.

Cytokine response and reactive oxygen species production after low- and intermediate-risk surgery.

BACKGROUND: Cytokines are secreted locally in response to surgery and may be released into the systemic circulation. Reactive oxygen species (ROS) production is involved in various inflammatory conditions. The aims of the study were to examine the magnitude of surgical stress on the modulation of immune response and ROS production. METHODS: Patients undergoing low- and intermediate-risk surgery (n=32) were enrolled. Blood samples for tumor necrosis factor (TNF)α, interleukin (IL)1ß and IL10 assays were obtained before anesthesia, immediately after extubation, at 24 and 72 h after surgery. Measurement in whole-blood cultures of ex vivo lipopolysaccharide (LPS) and Staphylococcus aureus Cowan (SAC)-stimulated production of cytokines was carried out. The pro-oxidant potency of the whole serum was assessed in human umbilical vein endothelial cells using a fluorescent probe after stimulation by the plasma collected at the same time intervals. RESULTS: TNFα, IL1ß and IL10 did not increase significantly after surgery in either group. Whole-blood cultures response to LPS and SAC stimulation decreased for IL1ß at the end of surgery in the two groups and returned to normal within 24 h after surgery. LPS- and SAC-induced IL10 production increased significantly at 24 h in the low-risk surgery group. ROS production was greater after more stressful surgery and was correlated to morphine consumption. CONCLUSION: Cytokine release in the systemic circulation was not well correlated to the magnitude of surgical stress, whereas transient immune hyporesponsiveness was seen after moderately stressful surgery. ROS production might be a more accurate indicator of the severity of surgical trauma.

[Drugs for status epilepticus treatment]. / Pharmacologie des agents utilisés dans l'état de mal épileptique.

The pharmacokinetics and pharmacodynamics of major antiepileptic agents are presented. The onset of action and the factors leading to extraction across the blood brain barrier are described as well as the mechanism and extent of metabolism, and the main interactions with other drugs. For each class, the dosing scheme and practical issues related to administration are described, based on evidence when available in the literature.

[Pre-peritoneal continuous infusion of local anesthetics for pain relief after laparotomy. A preliminary report]. / Infiltration continue prépéritonéale d'anesthésiques locaux pour l'analgésie après laparotomie. Données préliminaires.

INTRODUCTION: Continuous administration of local anesthetic through a catheter placed in the scar of a laparotomy is a postoperative analgesic technique, which seems effective but remains little developed and poorly codified. METHODS: In this prospective evaluation, we present a series of 25 observations of adult patients scheduled for abdominal laparotomy, to which a multiperforate catheter was placed at the end of the intervention by the surgeon in pre-peritoneal position, allowing the continuous perfusion of ropivacaïne over the first 48 postoperative hours. Patients received intravenous paracetamol associated with ketoprophene or nefopam. Opiates were given as rescue analgesics, in case of failure in pain relief, defined on objective criteria measured on visual analogic scale (VAS). RESULTS: The feasibility of the technique was excellent, except in one case of catheter obstruction. Pain was adequately relieved, with a majority of patients having VAS scores lower than 3/10 cm with the VAS, as well as rest as during mobilization. Only 9 patients needed morphine rescue analgesics. There was no sign of clinical overdose nor parietal complication related to the technique. Blood dosages of ropivacaine, carried out among 5 patients having received 600 mg daily, showed serum concentrations below the thresholds of toxicity. CONCLUSIONS: These results reveal a good effectiveness of the method, with moderate pain intensity and a low analgesic consumption. The local and general tolerance was excellent.

[Local anaesthetics: what can the pure S enantiomers contribute?]. / Anesthésiques locaux: qu'apportent les formes lévogyres?

The use of levobupivacaine and of ropivacaine may increase the safety of regional anaesthesia. These pure enantiomers have similar pharmacokinetic properties as those of the racemic mixtures. However, they are less cardiotoxic than the racemic mixtures, especially at the high heart rate usually encountered in infants. We may then recommend the use of these agents in the paediatric patients.

Extrahepatic metabolism of morphine occurs in humans.

The pharmacokinetics of morphine was studied in six patients in whom a radiologic localization of an insulinoma was to be performed under general anesthesia. Sampling was done in the peripheral artery, the mesenteric vein in five of the six patients, the hepatic vein, and the peripheral vein, as well as in urine. Hepatic blood flow was estimated by an indocyanine green infusion technique at the end of the radiologic procedure. Morphine terminal half-life was 92 +/- 9 minutes, total body clearance was 1260 ml.min-1, and the hepatic extraction ratio was 0.65 +/- 0.11. No concentration gradient was observed between the artery and the superior mesenteric vein, showing that no gut wall metabolism of morphine occurred. The total body clearance exceeded the hepatic clearance by 38%. It was concluded that the extrahepatic extraintestinal clearance of morphine probably occurred through the kidney.

Myocardial uptake of lignocaine: pharmacokinetics and pharmacodynamics in the isolated perfused heart of the rabbit.

1. The uptake kinetics and pharmacodynamics of lignocaine were studied in isolated perfused heart of the rabbit. 2. Six hearts were perfused with increasing concentrations of lignocaine in a modified Krebs-Henseleit buffer. The effluent concentration together with the increase in QRS duration were measured during lignocaine infusion and during 20 min after cessation of lignocaine infusion. 3. Lignocaine disposition and elimination were best described by a two-compartment open model. Terminal half-life was 11.0 +/- 2.9 min. The unidirectional transfer was slower from central to peripheral compartment than from peripheral to central compartment (T1/2.12 = 42.6 +/- 10.5 min whereas T1/2.21 = 10.7 +/- 2.8 min). The myocardium/perfusate concentration-ratio was 4.7 +/- 0.4. 4. The pharmacodynamic effect was best described in the central compartment by using the Hill equation. Calculated maximum QRS duration (Emax) was 77 +/- 8 ms. Emax was also directly measured in four additional rabbits by infusing ten times the dose of lignocaine used in the main experiment: the value of Emax measured in these conditions was 92.5 +/- 9.6 ms, i.e. a QRS widening of 150%. The steady-state perfusate concentration producing half the effect (C50) was 15.7 +/- 7.6 micrograms ml-1. 6. In conclusion, the specific lignocaine binding leading to increase in QRS duration appeared to be more closely related to the vascular stream than non specific binding leading to a deeper accumulation process.

Effects of halothane on the membrane potential in skeletal muscle of the frog.

Halothane has many effects on the resting membrane potential (V(m)) of excitable cells and exerts numerous effects on skeletal muscle one of which is the enhancement of Ca(2+) release by the sarcoplasmic reticulum (SR) resulting in a sustained contracture. The aim of this study was to analyse the effects of clinical doses of halothane on V(m), recorded using intracellular microelectrodes on cleaned and non stimulated sartorius muscle which was freshly isolated from the leg of the frog Rana esculenta. We assessed the mechanism of effects of superfused halothane on V(m) by the administration of selective antagonists of membrane bound Na(+), K(+) and Cl(-) channels and by inhibition of SR Ca(2+) release. Halothane (3%) induced an early and transient depolarization (4.5 mV within 7 min) and a delayed and sustained hyperpolarization (about 11 mV within 15 min) of V(m). The halothane-induced transient depolarization was sensitive to ryanodine (10 microM) and to 4-acetamido-4'-isothiocyanatostilbene 2,2' disulphonic acid (SITS, 1 mM). The hyperpolarization of V(m) induced by halothane (0.1 - 3%) was dose-dependent and reversible. It was insensitive to SITS (1 mM), tetrodotoxin (0.6 microM), and tetraethylammonium (10 mM) but was blocked and/or prevented by ryanodine (10 microM), charybdotoxin (CTX, 1 microM), and glibenclamide (10 nM). Our observations revealed that the effects of halothane on V(m) may be related to the increase in intracellular Ca(2+) concentration produced by the ryanodine-sensitive Ca(2+) release from the SR induced by the anaesthetic. The depolarization may be attributed to the activation of Ca(2+)-dependent Cl(-) (blocked by SITS) channels and the hyperpolarization to the activation of large conductance Ca(2+)-dependent K(+) channels, blocked by CTX, and to the opening of ATP-sensitive K(+) channels, inhibited by glibenclamide.

Effect of lignocaine in myocardial contusion: an experiment on rabbit isolated heart.

1. The reported incidence of myocardial contusion after blunt chest trauma varies from 16 to 76%. Of these patients, about 6% present a severe, life threatening contusion. We used an isolated heart preparation to examine the effect of lignocaine on myocardial performance after contusion. 2. Thirty hearts obtained from male New Zealand rabbits were perfused at constant flow according to the Langendorff technique and were divided into four groups. The following parameters were measured at frequent intervals for 60 min: mean coronary perfusion pressure (CPP), left ventricular diastolic pressure (LVDP), developed pressure (DP), dP/dtmax, dP/dtmin. 3. Group 1 (n = 6) served as control, group 2 (n = 7) received lignocaine for 20 min (15 microM for the first 10 min and 30 microM for the following 10 min), group 3 (n = 9) had a contusion leading to a 30-50% decrease in dP/dtmax and group 4 (n = 8) had the contusion and the lignocaine infusion was started 10 min after the contusion and stopped after 30 min. Lignocaine concentration was measured in the effluent. 4. Lignocaine alone moderately decreased contractility in group 2. In group 3, after contusion, DP, dP/ dtmax, and dP/dtmin were markedly decreased during the 60 min recording period. In group 4, lignocaine infusion rapidly restored contractility. DP, dP/dtmax and dP/dtmin returned towards their basal values. This improvement of contractility remained stable, even after lignocaine infusion was discontinued. 5. In our rabbit isolated heart preparation, lignocaine at a low therapeutic concentration was able to restore contractility after contusion. These results need to be confirmed by other studies but this may lead to promising therapeutic intervention.

Comparison of dopamine and norepinephrine after traumatic brain injury and hypoxic-hypotensive insult.

After severe brain trauma, blood-brain barrier disruption and alteration of cerebral arteriolar vasoreactive properties may modify the cerebral response to catecholamines. Therefore, the goal of the present study was to compare the effects of dopamine and norepinephrine in a model of brain injury that consisted of a weight-drop model of injury complicated by a 15-min hypoxic-hypotensive insult (HH). Sprague-Dawley rats (n = 7 in each group) received, after brain injury, an infusion of either norepinephrine (TNE group) or dopamine (TDA group) in order to increase cerebral perfusion pressure (CPP) above 70 mm Hg. In addition, a control group (C group, no trauma) and a trauma group (T group, brain injury, no catecholamine infusion) were studied. Mean arterial pressure (MAP), intracranial pressure (ICP, intraparenchymal fiberoptic device), and local cerebral blood flow (LCBF, extradural laser-Doppler fiber) were measured throughout the protocol. In T group, brain injury and HH induced a decrease in CPP (by an increase of ICP and a decrease of MAP), and a decrease of LCBF. Both norepinephrine and dopamine failed to increase CPP, and ICP was significantly higher in TNE and TDA groups than in T group. Interestingly, norepinephrine was not able to alleviate the decrease in MAP. Neither norepinephrine or dopamine could induce an increase of MAP. LCBF decreased similarly in T, TNE and TDA groups. In conclusion, norepinephrine and dopamine are not able to restore values of CPP above 70 mm Hg in a model of severe brain trauma. Furthermore, their systemic vasopressor properties are altered.

Postoperative pain after local anesthetics for laparoscopic sterilization.

OBJECTIVE: To test the effectiveness of intraperitoneal local anesthesia in relieving postoperative pain after laparoscopic sterilization. METHODS: In a double-blind, placebo-controlled randomized study of two groups of 25 subjects each, women scheduled for tubal sterilization under general anesthesia received 80 mL of 0.5% lidocaine with 1/320,000 epinephrine intraperitoneally in the right subdiaphragmatic quadrant at the beginning of the procedure. At the end of the procedure, they received 10 mL of 2% lidocaine with 1/80,000 epinephrine injected into each mesosalpinx. Controls received saline instead of lidocaine. Shoulder and pelvic pain assessed by visual analogue pain scale, postoperative analgesic requirements, nausea or vomiting, and time to return to normal daily activities were evaluated in the ambulatory unit and after discharge during the first 48 postoperative hours. Blood samples were taken in ten subjects receiving lidocaine to evaluate peak plasma concentrations and time to peak plasma concentrations. RESULTS: Pain was significantly less in patients who received lidocaine, and the difference lasted for the duration of the study (P < .05). Analgesic requirements and time to return to normal daily activities were significantly reduced in patients who received lidocaine (P < .05). Blood samples revealed no toxic concentrations. The peak plasma concentration was 3.22 +/- 1.21 micrograms/mL, and the time to peak plasma concentration was 42 +/- 15 minutes. CONCLUSION: Intraperitoneal instillation of lidocaine-epinephrine combined with mesosalpinx infiltration of lidocaine during tubal sterilization produces effective, long-lasting analgesia and improves the postoperative course.

Adverse effects of regional anaesthesia in children.

True complications of regional block procedures pertain to the performance of the block technique and the local anaesthetic. Such complications include lesions caused by the device used, and many of these complications can be avoided by using specifically designed devices.Complications related to the local anaesthetic solution mainly consist of local and systemic complications. Local toxicity has mainly been reported in adults following spinal administration of 5% lidocaine (lignocaine), a drug that is not usually used in children. Systemic toxicity consists of CNS and cardiovascular complications, methaemoglobinaemia and allergic reactions. Systemic toxicity has special features in children, especially in those <1 year old. Infants have a much higher free serum concentration of local anaesthetics than older children and adults, and are more prone to the deleterious effects of local anaesthetics. Additionally, as regional blocks are usually performed under general anaesthesia in children, signs of CNS toxicity may be concealed. Because of their higher heart rate, newborns and infants are thought to be more prone to the phasic block produced by tertiary amine agents such as bupivacaine than are adults. Serum concentrations at which bupivacaine (and etidocaine) exert cardiac toxicity seem to be similar to those producing CNS toxicity. As there is an increased threshold for CNS toxicity in infants plus an increased (or equal) sensitivity to bupivacaine cardiotoxicity, cardiac signs may not be preceded by any sign of CNS toxicity. Cardiac complications include: (i) arrhythmias with high degree conduction block, major QRS widening, torsade de pointes, and ventricular tachycardia related to re-entry phenomena; and (ii) major vascular collapse favoured by a concomitant decrease in the myocardial contractile force. Other complications of regional block procedures result from poor selection of agent, and inadequate safety precautions and monitoring of the patient, especially during the postoperative period. There are 2 other groups of disorders often reported as complications of regional anaesthetics: (i) effects that were not anticipated by the anaesthetist because of a lack of knowledge of all the consequences of the technique used; and (ii) complications attributed to a concomitant regional block procedure but with no established, sometimes even improbable, causal link with the regional technique. The overall morbidity of regional anaesthesia in children is low. Sound selection of local anaesthetics, insertion routes and block procedures, together with appropriate and careful monitoring, should prevent any major undesirable effects and enable regional anaesthesia to be a well tolerated and effective tool to overcome pain associated with minimal morbidity.

Resveratrol decreases hyperalgesia induced by carrageenan in the rat hind paw.

The effect of resveratrol, an aryl hydrocarbon receptor (AhR) antagonist, known to inhibit inducible cyclooxygenase-2 (COX2) and its transcription were examined in a model of hyperalgesia induced by carrageenan in the rat. Pretreatment with resveratrol did not reverse swelling and edema, but reversed the hyperalgesia induced by local tissue injury provoked by carrageenan. This reversal, occurring at resveratrol concentrations as low as 2 mg/kg, lasted for at least 48 hours. The link with COX2 activity inhibition and COX2 gene transcription, as well as a potential AhR inhibitory effect, remain to be established.

Additivity of bupivacaine and morphine for peripheral analgesia in rats.

Infiltration of the surgical wound is a classical technique for post-operative analgesia. Recent studies have suggested that local anaesthetic may be combined with other drugs such as opioids. This study has evaluated, in rat, the infiltration with morphine, bupivacaine and their combination. In all groups, the two hind paws were injected with carrageenin. The left hind paw was used as control. The vocalisation threshold to paw pressure (VTPP) of both hind paws was evaluated 2 h after induction of carrageenin inflammation (baseline value), then every 10 min until the return to baseline value after injection of analgesic drugs. The development of oedema was evaluated in both hind paws by measurement of paw circumference (PC) before, then after, carrageenin injection. All analgesic drugs were injected in the right inflamed paw diluted in 0.2 mL of normal saline. The analgesic effect of bupivacaine (0.1, 0.25 and 0.5%), morphine (25, 50 and 100 microg) and their combination (bupivacaine 0.1%/morphine 20 microg, bupivacaine 0.2%/morphine 40 microg and bupivacaine 0.4%/morphine 80 microg) was tested. The effect of naloxone on morphine induced analgesia was tested. The interaction between bupivacaine and morphine was evaluated with an isobolographic analysis. Bupivacaine produced a dose-dependent antinociceptive effect. Morphine infiltration produced a peripheral, dose-dependent analgesic effect antagonised by naloxone. This analgesic effect of morphine was associated with an anti-inflammatory effect. The isobolographic analysis revealed only additivity between bupivacaine and morphine. The infiltration with morphine offers a peripheral analgesic effect which is additive with the effect of bupivacaine. An anti-inflammatory effect of morphine participates in this peripheral analgesic effect.

Effect of CO(2) pneumoperitoneum on early cellular markers of retinal ischemia in rabbits with alpha-chymotrypsin-induced glaucoma.

BACKGROUND: Increased intraperitoneal pressure in the head-down position is associated with a significant increase in intraocular pressure (IOP) in rabbits with alpha-chymotrypsin-induced glaucoma. Also, the retinal cells are weakened by the induction of increased IOP, and/or glaucoma, even when IOP is controlled by adequate therapy; therefore, these cells need to be protected from any additional aggression. Actin and vimentin are proteins of the retinal cell cytoskeleton that react readily in response to retinal injuries, including ischemia and glaucoma. Early changes in these cytoskeleton proteins determine the morphological changes observed after retinal damage. Therefore, we set out to investigate intracytoplasmic changes in vimentin and actin after a 4-h CO(2) pneumoperitoneum in the head-down position in rabbits with alpha-chymotrypsin-induced glaucoma. METHODS: Twenty-one rabbits with alpha-chymotrypsin-induced glaucoma in one eye received general anesthesia for 4 h in the head-down position and were randomly allocated to have (a) no pneumoperitoneum, (b) a 10 mmHg CO(2) pneumoperitoneum, or (c) a 20 mmHg CO(2) pneumoperitoneum. At the end of the trial, both the right glaucomatous and the left control eyes were enucleated and investigated immunocytochemically for alterations in vimentin and actin, and morphologically for retinal layer disorganization. RESULTS: Except for the preexisting morphological changes induced by glaucoma, both the control and the glaucomatous eyes in all rabbits appeared normal in terms of retinal layer organization and the distribution of intracellular vimentin and actin whatever the intraperitoneal pressure level applied. CONCLUSION: In rabbits with alpha-chymotrypsin-induced glaucoma, a 4-h CO(2) pneumoperitoneum of