Severity of Myasthenia Gravis Influences the Relationship between Train-of-four Ratio and Twitch Tension and Run-down of Rat Endplate Potentials.

BACKGROUND: Train-of-four ratio (TOFR) is often used to evaluate muscle relaxation caused by neuromuscular-blocking agents (NMBAs). However, it is unknown whether TOFR reliably correlates with the first twitch tension (T1) in patients with myasthenia gravis (MG). By using rat models of experimental autoimmune MG (EAMG), the authors verified the hypothesis that the severity of MG influences the relationship between TOFR and T1. METHODS: EAMG rats were divided into sham, moderate MG, and severe MG groups. Isometric twitch tension of the hemidiaphragm was elicited by phrenic nerve stimulation with and without use of the NMBA rocuronium to measure TOFR and T1, and run-down of endplate potentials was estimated in the three groups. Changes around the neuromuscular junction in EAMG rats were investigated by observation of electron micrographs. RESULTS: With similar attenuation of T1, TOFR was significantly (n = 6) different among the three groups in the presence of 50% inhibitory concentrations of rocuronium (IC50). Run-down in the sham group was significantly (n = 8) greater with exposure to IC50, whereas that in the severe MG group was statistically insignificant. Width of the primary synaptic cleft in the severe MG group was significantly (n = 80) greater than that in the other groups. CONCLUSIONS: Severity of MG influences the relationship between TOFR and T1, together with changes in run-down of endplate potentials and those around the neuromuscular junction in rats. TOFR may, therefore, not be an accurate indicator of recovery from NMBAs in MG patients.

Stroke volume-directed administration of hydroxyethyl starch (HES 130/0.4) and Ringer's acetate in prone position during neurosurgery: a randomized controlled trial.

PURPOSE: General anesthesia in the prone position is associated with hypotension. We studied stroke volume (SV)-directed administration of hydroxyethyl starch (HES 130 kDa/0.4) and Ringer's acetate (RAC) in neurosurgical patients operated on in a prone position to determine the volumes required for stable hemodynamics and possible coagulatory effects. METHODS: Thirty elective neurosurgical patients received either HES (n = 15) or RAC (n = 15). Before positioning, SV measured by arterial pressure waveform analysis was maximized by fluid boluses until SV did not increase more than 10 %. SV was maintained by repeated administration of fluid. RAC 3 ml/kg/h was infused in both groups. Thromboelastometry assessed coagulation. Mann­Whitney U test, Wilcoxon signed-rank test, ANOVA on ranks, and a linear mixed model were applied. RESULTS: Comparable hemodynamics were achieved with the mean cumulative (SD) boluses of HES or RAC 240 (51) or 267 (62) ml (P = 0.207) before positioning, 340 (124) or 453 (160) ml (P = 0.039) 30 min after positioning, and 440 (229) or 653 (368) ml at the end of surgery (P = 0.067). The mean dose of basal RAC infusion was 813 (235) and 868 (354) ml (P = 0.620) in the HES and RAC group, respectively. Formation and maximum strength of the fibrin clot were decreased in the HES group. Intraoperative blood loss was comparable between groups (P = 0.861). CONCLUSION: The amount of RAC needed in the prone position was 25 % greater. The cumulative dose of 440 ml HES induced a slight disturbance in fibrin formation and clot strength. We suggest cautious administration of HES during neurosurgery.

Intravenous lipid emulsion only minimally influences bupivacaine and mepivacaine distribution in plasma and does not enhance recovery from intoxication in pigs.

BACKGROUND: The reported successful use of IV lipid emulsions in local anesthetic intoxications is thought to be due to lipid sequestration of local anesthetics. However, controlled efficacy studies were lacking, and other mechanisms of action have also been suggested. We investigated the effect of lipid infusion on plasma concentrations and cardiovascular effects of 2 local anesthetics differing in lipophilicity, bupivacaine, and mepivacaine. METHODS: Bupivacaine (n = 20) or mepivacaine (n = 20) was infused into a central vein of anesthetized (isoflurane 1%, Fio(2) 0.21) pigs until mean arterial blood pressure decreased to 50% from baseline. Isoflurane was discontinued and Fio(2) was increased to 1.0. Ten pigs in each local anesthetic group were treated with 20% lipid emulsion (ClinOleic®), and 10 pigs with Ringer's solution: 1.5 mL/kg in 1 minute followed by an infusion of 0.25 mL · kg(-1) · min(-1) for 29 minutes. Five additional pigs were infused bupivacaine and Intralipid®. Total and nonlipid-bound local anesthetic concentrations were determined from repeated blood samples. RESULTS: There were no overall differences in total or nonlipid-bound plasma local anesthetic concentrations between the lipid and Ringer's groups. However, plasma median total bupivacaine concentration was 21% and 23% higher at 20 and 30 minutes, respectively, in the lipid group (P = 0.016 without Holm-Bonferroni correction). There was also no overall difference between lipid and Ringer's groups in the rate of recovery of hemodynamic and electrocardiographic variables. Median mean arterial blood pressure in the lipid group with bupivacaine intoxication was 16 mm Hg and 15 mm Hg higher than in the corresponding Ringer's group at 10 and 15 minutes, respectively (P = 0.016 and P = 0.021, respectively, without Holm-Bonferroni correction). Intralipid® also caused no difference between total plasma and nonlipid-bound concentrations of bupivacaine with no apparent enhancement of recovery. CONCLUSIONS: Lipid emulsion neither had any measurable effect on the disposition of the studied local anesthetics in plasma, nor did it improve the rate of recovery from intoxication by either local anesthetic as measured by hemodynamic variables.

Pralidoxime inhibits paraoxon-induced depression of rocuronium-neuromuscular block in a time-dependent fashion.

OBJECTIVE: The composite effects of organophosphorus (OP)-cholinesterase (ChE) inhibitors and oximes on the actions of nondepolarizing neuromuscular blockers in acute OP-ChE inhibitor intoxication have not been evaluated in detail. We investigated the effects of paraoxon (Pox) (an OP-ChE inhibitor) and pralidoxime (PAM) (an oxime) on the nondepolarizing neuromuscular blocking action of rocuronium. METHODS: Isometric twitch tensions of rat left phrenic nerve-hemidiaphragm preparations elicited by indirect (phrenic nerve) supramaximal stimulation at 0.1 Hz were evaluated. Analysis of variance with post hoc testing was used for statistical comparison, and P < .05 was accepted as significant. RESULTS: Rocuronium reduced the indirectly elicited twitch tensions in normal (50% inhibitory concentration [IC(50)], 9.84 [9.64-10.04] µM, mean [95% confidence interval]) and all pretreated diaphragms (P < .01, n = 6) in a concentration-dependent fashion. Paraoxon caused a rightward shift in the rocuronium concentration-twitch tension curve (IC(50), 15.48 [15.24-15.72] µM). The rightward shift was completely inhibited by previous copretreatment (IC(50), 9.98 [9.77-10.20] µM) and partially inhibited by simultaneous copretreatment (IC(50), 11.68 [11.45-11.91] µM) with PAM but was not inhibited by subsequent copretreatment (IC(50), 13.69 [13.39-13.99] µM) with PAM (P < .01, n = 6). Atropine did not influence the rightward shift (P < .01, n = 6). DISCUSSION: Paraoxon depressed rocuronium-induced neuromuscular block by inhibiting ChEs, and the action of Pox was inhibited by PAM. Pralidoxime acts more intensely when applied earlier. The time-dependent effect of PAM indicates that the preceding presence of PAM in proximity to ChEs before Pox is necessary for definite suppression of the Pox-induced ChE inhibition.

Ultrasound-guided supraclavicular central venous catheterization in patients with malignant hematologic diseases.

We present two cases of central venous catheterization (CVC) in which an ultrasound-guided in-plane approach was used. Case 1 was a 60-year-old man with acute myelogenous leukemia in whom a right supraclavicular CVC was performed. He had pancytopenia (leukocytes 2,000/µL; erythrocytes 350 × 10(4)/µL; platelets 5.6 × 10(4)/µL), and abnormal coagulability (prothrombin time-international normalized ratio 1.35). A linear array transducer was positioned cephalad to the right clavicle and rotated 30° clockwise. The 21-gauge needle was manipulated from outside of the transducer. A CV catheter (CV legaforce EX(®); Terumo Co., Japan) was placed and stitched near the right clavicle. The patient felt no discomfort caused by the catheter. Case 2 was a 64-year-old women with malignant lymphoma whose right internal jugular vein was surrounded by abnormally enlarged lymph nodes. CVC was performed by the in-plane supraclavicular approach, avoiding puncture of the lymph node. This novel CVC technique is useful to minimize the risk of complications and patient discomfort by indwelling catheter.

Ultrasound-guided cervical nerve root block: spread of solution and clinical effect.

OBJECTIVES: We investigated the clinical effects and accuracy of ultrasound-guided cervical nerve root block. Additionally, spinal level and spread of injected solution were confirmed by anatomic dissection of fresh cadavers. DESIGN SETTING, PATIENTS, AND INTERVENTIONS: Twelve patients diagnosed with mono-radiculopathy between C5-7 underwent ultrasound-guided nerve root block. An insulated needle was advanced with an in-plane approach using nerve stimulation and 2 mL of 0.375% ropivacaine with 4 mg of dexamethasone was injected using nerve stimulation. Ultrasound-guided C5-7 nerve root block was also performed in ten fresh cadavers. Blue dye (2 mL) was injected onto each nerve root and anatomic dissection was performed to confirm the exact spinal level and spread pattern of the dye. RESULTS: Pain score before the procedure (65 [46-80], median [interquartile range]) was decreased to 25 [3-31] at 24 hours (P = 0.003) and 40 [28-66] at 30 days (P = 0.02) after the root block. Obvious side effects were not seen. All target nerve roots in patients and cadavers were correctly identified by ultrasound imaging. The needle tip did not reach the pedicle of the vertebral arch in the anteroposterior view of fluoroscopy, and spread pattern of contrast medium was extraforaminal and extraneural. CONCLUSIONS: This study suggests that injected solution by ultrasound-guided cervical nerve root block mainly spreads to the extraforaminal direction compared with conventional fluoroscopic technique. Therefore, present clinical study involves possibility of safer selective nerve root block with sufficient analgesic effects by ultrasound guidance, despite the absence of intraforaminal epidural spread of solution.

Comparison of hypertonic saline and mannitol on whole blood coagulation in vitro assessed by thromboelastometry.

BACKGROUND: Hypertonic saline (HS) is an alternative to mannitol for decreasing intracranial pressure in traumatic brain injury and before craniotomy. Both HS and mannitol may interfere with blood coagulation but their influence on coagulation has not been compared in controlled situations. Therefore, we evaluated different strengths of HS and 15% mannitol on blood coagulation in vitro. METHODS: Citrated fresh whole blood, withdrawn from 10 volunteers, was diluted with 0.9%, 2.5%, or 3.5% HS or 15% mannitol to make 10 vol.% and 20 vol.% hemodilution in vitro. The diluted blood and undiluted control samples were analyzed with thromboelastometry (ROTEM(®)) using two activators, tissue thromboplastin without (ExTEM(®)) or with cytochalasin (FibTEM(®)). RESULTS: In the FibTEM(®) analysis, maximum clot firmness (MCF) was stronger in the 2.5% HS group than in the mannitol group after both dilutions (P < 0.05). In the ExTEM(®) analysis, clot formation time (CFT) was more delayed in the mannitol group than in the 0.9%, 2.5%, or 3.5% HS groups in 20 vol.% hemodilution (P < 0.05). MCF was weaker in the mannitol group than in the other groups after 20 vol.% dilution (P < 0.05). MCF was also weaker in the 3.5% than in the 0.9% saline group after 20 vol.% dilution (P < 0.05). CONCLUSIONS: Blood coagulation is disturbed more by 15% mannitol than by equiosmolar 2.5% saline. This disturbance seems to be attributed to overall clot formation and strength but also to pure fibrin clot firmness. This saline solution might be more favorable than mannitol before craniotomy in patients with a high risk of bleeding.

Intravenous lipid emulsion sequesters amiodarone in plasma and eliminates its hypotensive action in pigs.

STUDY OBJECTIVE: Our objective is to investigate to what extent amiodarone is sequestered by intravenously administered lipid emulsion in plasma of pigs and whether the lipid emulsion inhibits amiodarone-induced hypotension. METHODS: Twenty anesthetized pigs received randomly 1.5 mL/kg bolus injection of olive/soybean oil-based 20% lipid emulsion (lipid group, n=10) or Ringer's acetate solution (control group, n=10) in 1 minute, followed by a continuous infusion of either solution for 30 minutes at 0.25 mL/kg per minute. Simultaneously with these continuous infusions, amiodarone hydrochloride was infused for 20 minutes at 1 mg/kg per minute in both groups. Plasma amiodarone concentration and mean arterial blood pressure were evaluated at predetermined intervals. RESULTS: Plasma amiodarone concentration in the lipid group increased more steeply during the amiodarone infusion than in the control group, at 20 minutes being a median 96.8 mg/L (interquartile range [IQR] 85.4, 102.0 mg/L) in the lipid group and median 21.5 mg/L (IQR 18.9, 22.3 mg/L) in the control group (difference 75.3 mg/L; 95% confidence interval [CI] 65.3 to 85.3 mg/L). After the separation of lipids from plasma by differential centrifugation, less amiodarone was contained in the lipid-poor aqueous fraction. At 20 minutes, the median was 13.3 mg/L (IQR 12.0, 13.7 mg/L), and the difference compared with the total plasma amiodarone concentration was -83.6 mg/L (95% CI -93.3 to -73.8 mg/L). In the lipid group, mean arterial blood pressure was not altered during the continuous amiodarone infusion. In the control group, mean arterial blood pressure decreased from baseline at 11 minutes, and the median was 52 mm Hg (IQR 51, 80 mm Hg) and the difference from baseline was 26 mm Hg (95% CI 9 to 43 mm Hg). Mean arterial blood pressure at 21 minutes also remained below the baseline, and the median was 57 mm Hg (IQR 50, 68 mm Hg) and the difference from baseline was 21 mm Hg (95% CI 9 to 33 mm Hg). CONCLUSION: Amiodarone was sequestered to a great extent by the intravenously administered lipids in plasma, which completely prevented the decrease in arterial blood pressure caused by amiodarone infusion. Further studies are needed to evaluate the clinical usefulness of intravenous lipid emulsion as an antidote in amiodarone overdoses.

[Optimal analgesic effect of continuous supraclavicular brachial plexus block with ropivacaine after shoulder surgery].

BACKGROUND: Optimal dose of local anesthetics for supraclavicular brachial plexus block (BPB) is still unknown. We prospectively investigated the analgesic effect of ultrasound-guided continuous supraclavicular BPB with ropivacaine at different infusion rates. METHODS: Thirty-nine patients scheduled to undergo shoulder surgery were randomly assigned to four groups; receiving no continuous BPB (control group, n = 10), BPB with 0.2% of ropivacaine at an infusion rate of 4 ml x hr(-1) (n = 12), BPB with 6 ml x hr(-1) (n = 12) or BPB with 8 ml x hr(-1) (n = 5). All patients were permitted to receive nonsteroidal anti-inflammatory drugs (NSAIDs) after surgery. Visual analogue scale (VAS) for postoperative pain was assessed and frequencies of the requirement of NSAIDs were recorded in each group. RESULTS: The pain scores during 24 hours after surgery in the 6 ml x hr(-1) group (3-24 mm) were significantly lower than those in the 4 ml x hr(-1) group (4-42 mm) and control group (6-56 mm). Mean frequency of administrations of NSAIDs for 24 hours after surgery in the 6 ml x hr(-1) (0.8 +/- 0.8) group was significantly lower than that in the control group (1.7 +/- 1.0). Continuous administration in two cases in the 8 ml x hr(-1) group was discontinued due to leakage of local anesthetics and headache. CONCLUSIONS: Continuous supraclavicular BPB with 0.2% ropivacaine at 6 ml x hr(-1) is effective for the pain management after shoulder surgery and is not an excess dose.

Lack in effects of therapeutic concentrations of dexmedetomidine and clonidine on the neuromuscular blocking action of rocuronium in isolated rat diaphragms.

BACKGROUND: We investigated the effects of the alpha-2 adrenoceptor agonists clonidine and dexmedetomidine on the neuromuscular blocking effect of rocuronium in vitro. METHODS: Isometric twitch tensions of rat nerve-hemidiaphragm preparations elicited by indirect (phrenic nerve) supramaximal stimulation at 0.1 Hz were evaluated. RESULTS: Clonidine and dexmedetomidine 50 microM (n = 6 each), but not 0.05 microM, shifted the rocuronium concentration-twitch tension curves to the left and decreased the rocuronium concentration for 50% twitch depression (IC50) compared with control (n = 9, P < 0.01). The leftward shift induced by clonidine 50 microM or dexmedetomidine 50 microM was not antagonized by yohimbine 50 microM, an alpha-2 adrenoceptor antagonist. Twitch tensions partially depressed by 7 microM rocuronium, to about 65% of the control, were further suppressed in a concentration-dependent manner by clonidine (n = 6) and dexmedetomidine (n = 9) at concentrations of 30 microM or more (P < 0.01). CONCLUSIONS: These results indicate that very high, but not therapeutic, concentrations of clonidine and dexmedetomidine enhance the neuromuscular blocking action of rocuronium, but this is not mediated by an agonist action on alpha-2 adrenoceptors.

Prone Versus Sitting Position in Neurosurgery-Differences in Patients' Hemodynamic Management.

OBJECTIVE: Neurosurgery in general anesthesia exposes patients to hemodynamic alterations in both the prone and the sitting position. We aimed to evaluate the hemodynamic profile during stroke volume-directed fluid administration in patients undergoing neurosurgery either in the sitting or the prone position. METHODS: In 2 separate prospective trials, 30 patients in prone and 28 patients in sitting position were randomly assigned to receive either Ringer acetate (RAC) or hydroxyethyl starch (HES; 130 kDa/0.4) for optimization of stroke volume. After combining data from these 2 trials, 2-way analysis of variance was performed to compare patients' hemodynamic profile between the 2 positions and to evaluate differences between RAC and HES consumption. RESULTS: To achieve comparable hemodynamics during surgery, a higher mean cumulative dose of RAC than HES was needed (679 mL ± 390 vs. 455 mL ± 253; P < 0.05). When fluid consumption was adjusted with weight, statistical difference was lost. Fluid administration did not differ between the prone and sitting position. Mean arterial pressure was lower and cardiac index and stroke volume index were higher over time in patients in the sitting position. CONCLUSIONS: The sitting position does not require excess fluid treatment compared with the prone position. HES is slightly more effective than RAC in achieving comparable hemodynamics, but the difference might be explained by patient weight. With goal-directed fluid administration and moderate use of vasoactive drugs, it is possible to achieve stable hemodynamics in both positions.

[The mechanisms of depression by benzodiazepines, barbiturates and propofol of excitatory synaptic transmissions mediated by adenosine neuromodulation].

Adenosine is known to modulate synaptic functions through adenosine receptors and the related adenosine neuromodulatory system. Benzodiazepines, barbiturates and propofol, the main actins of which are facilitation of GABAA receptor functions, also facilitate accumulation of endogenous adenosine in the extracellular space by inhibiting adenosine uptake via adenosine transporters. The accumulated adenosine depresses excitatory synaptic transmission by decreasing transmitter release, depressing postsynaptic sensitivity and inhibiting neuronal excitability through adenosine A1 receptors and the related adenosine neuromodulatory system. The adenosine-induced depressions of excitatory synaptic transmissions probably contribute to the mechanisms of the anesthetic, sedative, anticonvulsant and neuroprotective effects of these anesthetics and sedatives. An understanding of the synaptic mechanisms of these anesthetics and sedatives through the adenosine neuromodulatory system is needed for rational clinical use of the drugs.

[Anesthetic management for a radical operation in an infant with cloacal exstrophy].

We report the anesthetic management for a radical operation in an infant with cloacal exstrophy. Diagnosis of cloacal exstrophy with meningocele was made at the 26th week of gestation. Cesarian section was performed under general anesthesia in order to keep the infant in a state of apnea to prevent aerophagia, the so-called "sleeping baby", at the 38th week of gestation. As soon as the infant was born, she was intubated orotracheally and a radical operation (abdominal closure, removal of meningocele, and vesico-intestinal-pelvioplasty) was performed. Some complications occurred during the operation including hypotension, oliguria, hypothermia, hypoproteinemia, hyponatremia and hyperpotassemia. The operation time was 10 hours and 30 minutes. Mechanical ventilation was continued for 4 days in the NICU and the infant was discharged 37 days after the operation. Early prenatal diagnosis and simulation of the operation enabled an effective surgical procedure allowing us to minimize these intraoperative complications.

Blockers of adenosine A1, but not muscarinic acetylcholine, receptors improve excessive extracellular glutamate-induced synaptic depression.

We investigated adenosinergic and cholinergic effects on excessive glutamate-induced depressions of central excitatory synaptic transmissions in vitro. From the CA1 region in rat hippocampal slices, orthodromically elicited population spikes (PSs) and field excitatory postsynaptic potentials (fEPSPs) at 0.1Hz were simultaneously recorded. ANOVA was used for statistics, and p<0.05 was accepted as significant. Glutamate (10mM for 10min) completely depressed PSs and fEPSPs, which were partially recovered by the following washout for 40min (67.5±15.7% and 65.4±13.9% of the control, respectively, p<0.01, n=12). The recoveries in PSs and fEPSPs were exacerbated by edrophonium and carbamoylcholine but improved by non- and A1-selective adenosine receptor antagonists (p<0.01, n=6). The recovery in PSs, not that in fEPSPs, was exacerbated by adenosine, adenosine A1-receptor agonist and A2a-receptor antagonist (p<0.01, n=6). The effects of edrophonium were blocked by non-, M2- and M4-selective muscarinic acetylcholine receptor antagonists (p<0.01, n=6). Excessive glutamate depresses glutamatergic excitatory synaptic transmissions, which are exacerbated by muscarinic acetylcholine receptor stimulation but improved by adenosine A1 receptor block. Somatic excitability is impaired by excessive glutamate with adenosine A1 receptor stimulation.

No antidotal effect of intravenous lipid emulsion in experimental amitriptyline intoxication despite significant entrapment of amitriptyline.

Intravenous lipid emulsion has been used in the resuscitative treatment of intoxications caused by local anaesthetics and tricyclic antidepressants with seemingly beneficial results. We studied the effect of intravenous lipid emulsion on the plasma concentration of amitriptyline and haemodynamic recovery in a pig model of amitriptyline intoxication. Twenty pigs were anaesthetized (1% isoflurane in 21% O(2)) and given amitriptyline 15 mg/kg intravenously for 15 min. In random fashion immediately thereafter, either 20% lipid emulsion (ClinOleic(®), Lipid group) or Ringer's acetate (Control group) was infused for 30 min.; first 1.5 ml/kg for 1 min., followed by 0.25 ml/kg/min. for 29 min. The amitriptyline concentration in total and lipid-poor plasma and haemodynamic parameters were measured until 30 min. after the infusions. Lipid infusion prevented the decrease in plasma total amitriptyline concentration, resulting in a 90% higher (p < 0.001) total concentration and significantly (p = 0.014) lower free fraction of plasma amitriptyline in the Lipid group (1.1%) compared with the Control group (3.0%) at 30 min. Haemodynamic recovery from the intoxication as measured by heart rate, arterial pressure or cardiac output was similar in both groups. However, five pigs in the Lipid group and two pigs in the Control group died. In conclusion, a marked entrapment of amitriptyline by intravenous lipid emulsion was observed but this did not improve the pigs' haemodynamic recovery from severe amitriptyline intoxication. Care should be exercised in the antidotal use of lipid emulsion until controlled human studies indicate its efficacy and safety.

Effect of arterial blood pressure on the arterial to end-tidal carbon dioxide difference during anesthesia induction in patients scheduled for craniotomy.

BACKGROUND: Before obtaining results of arterial blood gas analysis in mechanically ventilated patients undergoing neurosurgery, the volume of ventilation is primarily adjusted according to endtidal CO2 (EtCO2). We characterized the impact of various arterial blood pressure changes on arterial PCO2 (PaCO2) to EtCO2 differences (PaCO2-EtCO2) in patients anesthetized for craniotomy. METHODS: Seventy-two elective craniotomy patients were enrolled in this prospective study. Noninvasive blood pressure was measured before anesthesia induction. Anesthesia was induced with thiopental, rocuronium or suxamethonium, and fentanyl and was maintained with inhaled anesthetics or propofol and remifentanil. Volume-controlled ventilation was adjusted after intubation according to the clinical judgment. The first arterial blood gas analysis was taken just before the head pinning. Systolic, diastolic, and mean arterial blood pressures (MAP) and heart rate were registered after intubation every 5 minutes until the head pinning. RESULTS: PaCO2-EtCO2 correlated positively with percentage difference between MAP awake at arrival in operating room and during arterial CO2 determination (P=0.0008, r=0.388). In analysis according to a MAP decrease of less than 20% (n=17), 20% to 29% (n=24), 30% to 35% (n=16), and more than 35% (n=15), the mean (SD) PaCO2-EtCO2 was greater in patients with MAP decrease of over 35% or 30% to 35% than in patients with MAP decrease of less than 20%. The mean (SD) absolute values of the PaCO2-EtCO2 were 0.96 (0.43) kPa or 0.85 (0.31) kPa versus 0.55 (0.24) kPa, respectively (P<0.05 between categories). Mean EtCO2 was not different in the various MAP difference categories, but PaCO2 was greatest when MAP decreased more than 35% (P<0.05). CONCLUSIONS: There was a positive correlation between PaCO2-EtCO2 and MAP decrease shortly after induction of anesthesia. PaCO2-EtCO2 is recommended to be interpreted together with change in MAP during early phase of neuroanesthesia to guarantee optimal mechanical ventilation.

Effects of atropine and pralidoxime on neuronal actions of paraoxon in rat hippocampal slices.

The actions of paraoxon, an organophosphorus cholinesterase (ChE) inhibitor, on central synaptic transmission and somatic excitability, and the inhibitory effects of atropine, a non-selective muscarinic acetylcholine receptor (mAChR) antagonist, and pralidoxime (PAM), an oxime, on these actions were investigated. From rat hippocampal slices, CA1-population spikes (PSs) and CA1-field excitatory postsynaptic potentials (fEPSPs) at 0.1Hz were recorded using a multi-electrode array (MEA) system. Statistics were performed using ANOVA with Bonferroni/Dunn testing (n=6 in all data). Paraoxon (1µM) depressed fEPSPs but did not significantly influence PSs. The fEPSP depression was inhibited by pre-, simultaneous and post-treatments with atropine (10µM, p<0.01) and pre-treatment with PAM (10µM, p<0.01). The insignificance of the paraoxon-induced PS change was not altered by pre-, simultaneous and post-treatments with atropine or by pre- and post-treatments with PAM; however, PSs were significantly depressed by simultaneous treatment with paraoxon and PAM (p<0.01). Paraoxon-induced ChE inhibition depresses excitatory synaptic transmission and facilitates somatic excitability mediated by mAChRs, and the latter counteracts influence of the depressed synaptic transmission on somatic action potentials. Atropine and PAM prevent and depress the actions of paraoxon and are more effective with earlier treatment.

Sitting position for removal of pineal region lesions: the Helsinki experience.

OBJECTIVE: To present a summary of anesthetic considerations for use of the sitting position in procedures to remove lesions of the occipital and suboccipital regions, with a special reference to the Helsinki experience with more than 300 operations in 1997-2007, and a retrospective study evaluating the incidence of venous air embolism (VAE) and hemodynamic stability in patients operated in the steep sitting position. METHODS: Anesthesiology reports of 72 patients with a mean (± standard deviation [SD]) age of 33 years ± 18 treated by the senior author (J.H.) for pineal region tumors using the infratentorial supracerebellar approach in the sitting position during an 11-year period were retrospectively reviewed for the incidence of VAE and hemodynamic stability. RESULTS: In the sitting position, median systolic blood pressure changed -8 (-95 to +50) mm Hg without alteration in heart rate. Based on patient records, the incidence of VAE was 19% (14 of 72 patients). In five patients, end-tidal carbon dioxide (ETCO(2)) decreased more than 0.7 kPa (5.25 mm Hg), possibly indicating VAE. Comparing patients with and without VAE, no differences in change of blood pressure, heart rate, or amount of administered vasoactive agents were observed. Postoperative duration of ventilator treatment and hospital stay were similar in patients with and without VAE. No signs of arterial embolization were seen postoperatively. CONCLUSIONS: The sitting position is associated with risk for hypotension. The same surgical approach and procedure does not exclude the occurrence of VAE. In this study, the unaltered hemodynamics in patients during VAE indicates relatively small VAE. Possible explanations for this are early recognition of air leakage and good cooperation between the surgical and anesthesia teams.

Acute late sepsis attenuates effects of a nondepolarizing neuromuscular blocker, rocuronium, by facilitation of endplate potential and enhancement of membrane excitability in vitro.

BACKGROUND: Sepsis attenuates the muscle-relaxing effects of nondepolarizing neuromuscular blockers. The authors investigated the effects of acute late sepsis on neuromuscular transmission and neuromuscular actions of rocuronium to clarify the mechanisms by which sepsis attenuates the effects of nondepolarizing neuromuscular blockers. METHODS: Sepsis was induced by cecal ligation and puncture operation. Endplate potentials, acetylcholine potentials, and electrotonic potentials were recorded from the motor endplates of isolated diaphragms from acute late septic and nonseptic rats. RESULTS: (1) Sepsis did not influence the effect of rocuronium to decrease endplate potential amplitude, which was increased by sepsis itself; (2) sepsis facilitated the effect of rocuronium to decrease quantal acetylcholine release, which was increased by sepsis itself; (3) sepsis did not influence the effect of rocuronium to decrease acetylcholine sensitivity, which was decreased by sepsis itself; (4) sepsis decreased critical depolarization, and rocuronium did not influence critical depolarization. CONCLUSIONS: These results indicate that acute late sepsis facilitates endplate potentials and enhances excitability of the muscle membrane, indicated by a decrease of critical depolarization. It is thought that these elicit the sepsis-induced attenuation of the muscle-relaxing effects of rocuronium.

Sepsis stage dependently and differentially attenuates the effects of nondepolarizing neuromuscular blockers on the rat diaphragm in vitro.

We investigated the effects of early and late sepsis on the actions of nondepolarizing neuromuscular blockers by using a rat sepsis model induced by cecal ligation and puncture. Isometric twitch tensions of nerve-hemidiaphragm preparations elicited by indirect (phrenic nerve) supramaximal stimulation at 0.1 Hz were evaluated. Rocuronium, pancuronium, and d-tubocurarine dose-dependently decreased the twitch tensions of the nonseptic, early septic, and late septic diaphragms (P < 0.01 each by analysis of variance [ANOVA]). Late sepsis shifted the concentration-twitch tension curves rightward from those of nonsepsis to larger degrees than did early sepsis, as indicated by increases in 50% inhibitory concentration (IC(50)) values (P < 0.01 each by ANOVA and P < 0.01 or 0.05 by the Scheffe F test). The standardized rightward shifts in early and late sepsis were largest for pancuronium, second largest for rocuronium, and smallest for d-tubocurarine (5.741, 2.979, and 1.660 times in late sepsis, respectively; P < 0.01 each by ANOVA and the Scheffe F test). Sepsis-induced increases in IC(50) values did not accompany the decreases in slopes. The results indicate that sepsis induces hyposensitivities to nondepolarizing neuromuscular blockers, the degree of which depends on the stage of sepsis and on the kind of neuromuscular blocker.