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1.
World Neurosurg ; 97: 261-266, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27744075

ABSTRACT

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.


Subject(s)
Blood Pressure/physiology , Disease Management , Hemodynamics/physiology , Neurosurgical Procedures/methods , Patient Positioning/methods , Prone Position/physiology , Adult , Aged , Female , Fluid Therapy/methods , Humans , Male , Middle Aged , Neurosurgical Procedures/adverse effects , Patient Positioning/adverse effects , Prospective Studies
2.
Anesthesiology ; 124(2): 369-77, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26569169

ABSTRACT

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.


Subject(s)
Excitatory Postsynaptic Potentials/physiology , Myasthenia Gravis/physiopathology , Neuromuscular Monitoring/methods , Androstanols/administration & dosage , Animals , Diaphragm/physiopathology , Disease Models, Animal , Female , Neuromuscular Junction/physiopathology , Neuromuscular Monitoring/statistics & numerical data , Neuromuscular Nondepolarizing Agents/administration & dosage , Rats , Rats, Inbred Lew , Rocuronium , Severity of Illness Index , Synaptic Transmission/physiology
3.
J Anesth ; 28(2): 189-97, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24077833

ABSTRACT

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.


Subject(s)
Hydroxyethyl Starch Derivatives/therapeutic use , Isotonic Solutions/administration & dosage , Plasma Substitutes/administration & dosage , Stroke Volume/drug effects , Adult , Aged , Blood Coagulation/drug effects , Female , Hemodynamics/drug effects , Humans , Hydroxyethyl Starch Derivatives/administration & dosage , Isotonic Solutions/therapeutic use , Male , Middle Aged , Neurosurgical Procedures/methods , Patient Positioning , Plasma Substitutes/therapeutic use , Prone Position , Thrombelastography
4.
Neurosci Res ; 75(2): 103-11, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23174314

ABSTRACT

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.


Subject(s)
Adenosine A1 Receptor Antagonists/pharmacology , Adenosine/antagonists & inhibitors , Excitatory Postsynaptic Potentials/drug effects , Receptors, Muscarinic/drug effects , Synaptic Transmission/drug effects , Acetylcholine/metabolism , Adenosine A1 Receptor Agonists/pharmacology , Animals , Glutamic Acid/pharmacology , Hippocampus/physiology , Neurons/drug effects , Rats , Rats, Wistar
5.
J Anesth ; 26(5): 775-8, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22547165

ABSTRACT

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.


Subject(s)
Catheterization, Central Venous/methods , Clavicle/diagnostic imaging , Leukemia, Myeloid, Acute/diagnostic imaging , Leukemia, Myeloid, Acute/surgery , Lymphoma/diagnostic imaging , Lymphoma/surgery , Ultrasonography, Interventional/methods , Female , Humans , Male , Middle Aged
6.
Am J Emerg Med ; 30(6): 901-7, 2012 Jul.
Article in English | MEDLINE | ID: mdl-21871755

ABSTRACT

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.


Subject(s)
Androstanols/antagonists & inhibitors , Cholinesterase Inhibitors/pharmacology , Cholinesterase Reactivators/pharmacology , Neuromuscular Nondepolarizing Agents/antagonists & inhibitors , Paraoxon/pharmacology , Pralidoxime Compounds/pharmacology , Androstanols/pharmacology , Animals , Diaphragm/drug effects , Diaphragm/physiology , Dose-Response Relationship, Drug , Drug Interactions , Male , Neuromuscular Nondepolarizing Agents/pharmacology , Paraoxon/antagonists & inhibitors , Phrenic Nerve/drug effects , Phrenic Nerve/physiology , Rats , Rats, Wistar , Rocuronium , Time Factors
7.
Anesth Analg ; 114(4): 901-6, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22025489

ABSTRACT

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.


Subject(s)
Anesthetics, Local/blood , Bupivacaine/blood , Fat Emulsions, Intravenous/pharmacology , Mepivacaine/blood , Animals , Bupivacaine/toxicity , Electrocardiography/drug effects , Emulsions/pharmacology , Female , Hemodynamics/drug effects , Male , Mepivacaine/toxicity , Phospholipids/pharmacology , Plant Oils/pharmacology , Soybean Oil/pharmacology , Swine
8.
Basic Clin Pharmacol Toxicol ; 110(4): 378-83, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22023355

ABSTRACT

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.


Subject(s)
Amitriptyline/poisoning , Antidepressive Agents, Tricyclic/poisoning , Antidotes/pharmacology , Fat Emulsions, Intravenous/pharmacology , Amitriptyline/pharmacokinetics , Animals , Antidepressive Agents, Tricyclic/pharmacokinetics , Blood Pressure/drug effects , Cardiac Output/drug effects , Female , Heart Rate/drug effects , Male , Random Allocation , Swine
9.
Pain Med ; 12(8): 1190-5, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21692976

ABSTRACT

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.


Subject(s)
Cervical Vertebrae/diagnostic imaging , Nerve Block/methods , Radiculopathy/drug therapy , Spinal Nerve Roots/diagnostic imaging , Ultrasonography, Interventional/methods , Aged, 80 and over , Amides/administration & dosage , Amides/pharmacology , Amides/therapeutic use , Anesthetics, Local/administration & dosage , Anesthetics, Local/pharmacology , Anesthetics, Local/therapeutic use , Cadaver , Dexamethasone/administration & dosage , Dexamethasone/pharmacology , Dexamethasone/therapeutic use , Female , Humans , Male , Pain/drug therapy , Pain Measurement , Ropivacaine , Spinal Nerve Roots/drug effects
10.
Neurocrit Care ; 14(2): 238-43, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21369792

ABSTRACT

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.


Subject(s)
Blood Coagulation/drug effects , Diuretics, Osmotic/pharmacology , Mannitol/pharmacology , Saline Solution, Hypertonic/pharmacology , Thrombelastography/drug effects , Adult , Brain Injuries/drug therapy , Brain Injuries/surgery , Craniotomy , Critical Care , Female , Humans , In Vitro Techniques , Male , Young Adult
11.
Masui ; 59(11): 1385-90, 2010 Nov.
Article in Japanese | MEDLINE | ID: mdl-21077306

ABSTRACT

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.


Subject(s)
Amides/pharmacology , Anesthetics, Local/pharmacology , Brachial Plexus , Nerve Block/methods , Shoulder Joint/surgery , Female , Humans , Male , Middle Aged , Prospective Studies , Ropivacaine
12.
Neurosci Res ; 68(4): 276-84, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20816709

ABSTRACT

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.


Subject(s)
Atropine/pharmacology , Cholinesterase Inhibitors/pharmacology , Cholinesterase Reactivators/pharmacology , Muscarinic Antagonists/pharmacology , Neurons/drug effects , Paraoxon/pharmacology , Synaptic Transmission/drug effects , Animals , Excitatory Postsynaptic Potentials/drug effects , Hippocampus/drug effects , Organ Culture Techniques , Patch-Clamp Techniques , Pralidoxime Compounds/pharmacology , Rats , Rats, Wistar
13.
Ann Emerg Med ; 56(4): 402-408.e2, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20868908

ABSTRACT

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.


Subject(s)
Amiodarone/antagonists & inhibitors , Fat Emulsions, Intravenous/pharmacology , Hypotension/chemically induced , Vasodilator Agents/antagonists & inhibitors , Amiodarone/adverse effects , Amiodarone/blood , Amiodarone/pharmacokinetics , Animals , Blood Pressure/drug effects , Female , Heart Rate/drug effects , Hypotension/prevention & control , Male , Oxygen/blood , Swine , Vasodilator Agents/adverse effects , Vasodilator Agents/blood , Vasodilator Agents/pharmacokinetics
14.
J Neurosurg Anesthesiol ; 22(4): 303-8, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20622686

ABSTRACT

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.


Subject(s)
Anesthesia, Inhalation , Blood Pressure/physiology , Carbon Dioxide/blood , Craniotomy , Blood Gas Analysis , Body Temperature , Female , Humans , Hydrogen-Ion Concentration , Intubation, Intratracheal , Male , Middle Aged , Neurosurgical Procedures , Prospective Studies , Respiration, Artificial , Respiratory Mechanics , Spirometry
15.
World Neurosurg ; 74(4-5): 505-13, 2010.
Article in English | MEDLINE | ID: mdl-21492603

ABSTRACT

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.


Subject(s)
Embolism, Air/etiology , Intracranial Hypotension/etiology , Neurosurgical Procedures/adverse effects , Patient Positioning/adverse effects , Pineal Gland/surgery , Pinealoma/surgery , Adolescent , Adult , Aged , Child , Child, Preschool , Embolism, Air/prevention & control , Embolism, Air/surgery , Female , Finland , Humans , Infant , Intracranial Hypotension/physiopathology , Intracranial Hypotension/prevention & control , Male , Middle Aged , Neurosurgical Procedures/methods , Neurosurgical Procedures/standards , Patient Positioning/methods , Patient Positioning/standards , Pineal Gland/pathology , Retrospective Studies
16.
Anesth Analg ; 104(5): 1116-20, tables of contents, 2007 May.
Article in English | MEDLINE | ID: mdl-17456661

ABSTRACT

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.


Subject(s)
Androstanols/pharmacology , Clonidine/administration & dosage , Dexmedetomidine/administration & dosage , Diaphragm/drug effects , Neuromuscular Blockade/methods , Animals , Clonidine/pharmacokinetics , Dexmedetomidine/pharmacokinetics , Diaphragm/physiology , Dose-Response Relationship, Drug , Drug Synergism , Male , Neuromuscular Nondepolarizing Agents/pharmacology , Rats , Rats, Wistar , Rocuronium
17.
Anesthesiology ; 105(5): 968-75, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17065891

ABSTRACT

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.


Subject(s)
Androstanols/pharmacology , Motor Endplate/drug effects , Motor Endplate/physiopathology , Neuromuscular Nondepolarizing Agents/pharmacology , Sepsis/physiopathology , Acute Disease , Animals , Electric Stimulation , Electrophysiology , In Vitro Techniques , Male , Membrane Potentials/drug effects , Rats , Rats, Wistar , Rocuronium , Synaptic Transmission/drug effects
18.
Masui ; 55(6): 684-91, 2006 Jun.
Article in Japanese | MEDLINE | ID: mdl-16780077

ABSTRACT

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.


Subject(s)
Adenosine/physiology , Barbiturates/pharmacology , Benzodiazepines/pharmacology , Neurotransmitter Agents/physiology , Propofol/pharmacology , Synaptic Transmission/drug effects , Adenosine/metabolism , Animals , Depression, Chemical , Humans , Mice , Receptors, Purinergic P1/physiology
19.
Anesth Analg ; 100(3): 823-829, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15728074

ABSTRACT

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.


Subject(s)
Neuromuscular Junction/drug effects , Neuromuscular Nondepolarizing Agents/pharmacology , Sepsis/physiopathology , Androstanols/pharmacology , Animals , Diaphragm , Dose-Response Relationship, Drug , In Vitro Techniques , Male , Muscle Contraction/drug effects , Neuromuscular Junction/physiology , Pancuronium/pharmacology , Rats , Rats, Wistar , Rocuronium , Tubocurarine/pharmacology
20.
Anesthesiology ; 102(1): 165-74, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15618800

ABSTRACT

BACKGROUND: The aim of this study was to determine whether halothane and isoflurane used during and after surgical injury attenuate subsequent hyperexcitability of spinal dorsal horn (SDH) neurons by preventing development of central sensitization. METHODS: Activity of a wide-dynamic-range neuron of the SDH was isolated in decerebrate-spinal Sprague-Dawley rats, and neuronal activity (receptive field size and responses to nonnoxious and noxious stimuli) was recorded. A 1-cm-long incision was made through the skin, fascia, and muscle under anesthesia with halothane (1.1% or 2.2%) and isoflurane (1.4% or 2.8%). Anesthesia was discontinued just after the incision had been made or was continued until 30 min after the incision, and activity of the SDH neurons was measured for up to 2 h after the incision. In a control group, the incision was made without anesthesia. RESULTS: In the control group, the incision resulted in maximum excitation in the SDH neurons during surgery; spontaneous activity significantly increased for up to 30 min after the incision (P < 0.05) but did not significantly increase thereafter, returning to the preincision value. Halothane and isoflurane suppressed excitation of the neurons during the incision in a concentration-related manner. Administration of 2.2% halothane and 2.8% isoflurane during the incision and for up to 30 min after the incision almost abolished activity of the neurons for 30 min after the incision. The magnitude of neuronal activity 2 h after the incision was not significantly different among all groups, including the control group. CONCLUSIONS: The results demonstrate that administration of halothane and isoflurane does not attenuate development of hyperexcitability of SDH neurons despite the fact that excitation and spontaneous activity during and after the incision were greatly suppressed by administration of halothane and isoflurane.


Subject(s)
Anesthetics, Inhalation/pharmacology , Halothane/pharmacology , Isoflurane/pharmacology , Posterior Horn Cells/drug effects , Posterior Horn Cells/physiology , Surgical Procedures, Operative/adverse effects , Animals , Blood Pressure/drug effects , Decerebrate State , Electrophysiology , Evoked Potentials/drug effects , Male , Mechanoreceptors/physiology , Microelectrodes , Physical Stimulation , Rats , Rats, Sprague-Dawley , Sutures/adverse effects
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