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Anesthetic-related cardiac arrest and its mortality: a report covering 72,959 anesthetics over 10 years from a US teaching hospital.

BACKGROUND: A prospective and retrospective case analysis study of all perioperative cardiac arrests occurring during a 10-yr period from 1989 to 1999 was done to determine the incidence, cause, and outcome of cardiac arrests attributable to anesthesia. METHODS: One hundred forty-four cases of cardiac arrest within 24 h of surgery were identified over a 10-yr period from an anesthesia database of 72,959 anesthetics. Case abstracts were reviewed by a Study Commission composed of external and internal members in order to judge which cardiac arrests were anesthesia-attributable and which were anesthesia-contributory. The rates of anesthesia-attributable and anesthesia-contributory cardiac arrest were estimated. RESULTS: Fifteen cardiac arrests out of a total number of 144 were judged to be related to anesthesia. Five cardiac arrests were anesthesia-attributable, resulting in an anesthesia-attributable cardiac arrest rate of 0.69 per 10,000 anesthetics (95% confidence interval, 0.085-1.29). Ten cardiac arrests were found to be anesthesia-contributory, resulting in an anesthesia-contributory rate of 1.37 per 10,000 anesthetics (95% confidence interval, 0.52-2.22). Causes of the cardiac arrests included medication-related events (40%), complications associated with central venous access (20%), problems in airway management (20%), unknown or possible vagal reaction in (13%), and one perioperative myocardial infarction. The risk of death related to anesthesia-attributable perioperative cardiac arrest was 0.55 per 10,000 anesthetics (95% confidence interval, 0.011-1.09). CONCLUSIONS: Most perioperative cardiac arrests were related to medication administration, airway management, and technical problems of central venous access. Improvements focused on these three areas may result in better outcomes.

Adolescent↗

Hemodynamics of anesthetized ventilated mouse models: aspects of anesthetics, fluid support, and strain.

This study evaluates the effects of anesthesia and fluid support on hemodynamic parameters of the mechanically ventilated mouse of four different strains. All experiments were performed at a similar surgical level of anesthesia, as indicated by the probing of the pedal withdrawal reflex. Three anesthetic regimens [fentanyl-fluanisone-midazolam (FFM), ketamine-medetomidine-atropine (KMA), and isoflurane (ISO)], four commonly used mouse strains (Swiss, CD-1, BalbC, and C57Bl6), and three different fluid support strategies (no fluid, 0.2 ml x h(-1) x 10 g(-1) of 6% polystarch solution, and 0.5 ml x h(-1) x 10 g(-1) saline) were studied. Mean arterial pressure (MAP) or heart rate (HR) was similar among the four strains of mice except a trend toward lower HR for the BalbC mice. In terms of MAP, KMA is the preferred anesthetic for the Swiss and CD-1 mice, whereas KMA or ISO are recommended for BalbC or C57Bl6 mice. In terms of HR, ISO is the preferred anesthetic for the Swiss, CD-1, and C57Bl6 strains. No differences in HR for the three anesthetics were observed for the BalbC strain. Compared with administration of no fluid, both saline and polystarch administration similarly increased MAP by 7 +/- 2, 10 +/- 2, and 11 +/- 2 mmHg at t = 1, 2, and 3 h, respectively, whereas fluid administration was without effect on HR. Saline supplementation resulted in an increased dry-to-wet ratio of the heart and both fluid regimens decreased total hemoglobin in the blood from 12.6 +/- 0.5 to 10.4 +/- 0.5 g/100 ml. Saline administration was associated with blood acidosis (pH 7.20 +/- 0.03) compared with the Haes (pH 7.29 +/- 0.02) or no-fluid group (pH 7.34 +/- 0.03), whereas PCO(2) was approximately 30 mmHg for all groups. We conclude that at similar surgical levels of anesthesia, the preferable type of anesthesia (ISO or KMA, but never FFM) depends on the strain used and whether MAP or HR is the focus of study. Additional fluid support is beneficial in terms of raising arterial blood pressure, although this is at the cost of changes in organ water content and increased anemia.

Anesthesia↗

During anesthetic-induced activation of hypothalamic pituitary adrenal axis, blood-borne steroids fail to contribute to the anesthetic effect.

Anesthetic doses of ethanol (100 mmol/kg p.o.), chloral hydrate (2 mmol/kg i.p.), and urethane (9 mmol/kg i.p.) induce sharp and sustained (6- to 10-fold) dose-dependent increase in rat brain pregnenolone and progesterone content. In contrast, other general anesthetics such as ketamine (0.7 mmol/kg i.p.) and pentobarbital (0.2 mmol/kg i.p.), and the sedative/hypnotic clonazepam (17 mumol/kg i.p.) decrease brain pregnenolone and progesterone content. The increase in brain pregnenolone and progesterone content fails to occur if ethanol, chloral hydrate, and urethane are administered to hypophysectomized-adrenalectomized rats suggesting that the increase of brain steroids requires the hypophysis and probably originates in peripheral tissues and not in brain. The administration to hypophysectomized rats of 5 IU/kg of ACTH produces a brain pregnenolone and progesterone accumulation by an extent comparable to that elicited by anesthetic doses of ethanol, chloral hydrate, or urethane in intact animals. However, the increase in brain pregnenolone and progesterone content induced by ACTH is devoid of anesthetic or sedative effects and does not appear to change central GABAergic tone. In fact, ACTH, unlike allopregnanolone and allodeoxicorticosterone, failed to delay the onset of isoniazid-induced seizures, to reduce the fear of novelty in the elevated plus maze test as inferred by the increase in the number of entries or the time spent in the open arm. Thus, the data suggest that blood-borne steroids cannot function as precursors of brain neurosteroid modulators acting on GABAA receptor.

Adrenal Glands↗

Effects of volatile anesthetics on the activity of laryngeal 'drive' receptors in anesthetized dogs.

Effects of halothane, isoflurane and sevoflurane on laryngeal drive receptor activity were studied in the afferent activity of the superior laryngeal nerve in anesthetized spontaneously breathing dogs. Of 40 single units recorded, most of them (65%) responded to the volatile anesthetics applied to the isolated larynx at a concentration of 5%. The exposure to the anesthetics resulted in either an inspiratory increase (15%), both inspiratory and expiratory decrease (54%), or both inspiratory increase and expiratory decrease (31%) responses. The average discharge frequency of the receptors tended to be decreased on inhalation of the anesthetics, where significant decreases were observed in both respiratory phases for halothane and at expiration for isoflurane, but in neither respiratory phase for sevoflurane. These results support an advantage of sevoflurane over halothane and isoflurane for induction of anesthesia to minimize the influence of the activity of laryngeal drive receptors on the breathing pattern and airway stability.

Anesthetics, Inhalation↗

The local anesthetic activity of saxitoxin alone and with vasoconstrictor and local anesthetic agents.

STX (saxitoxin), alone and with various vasoconstrictor and local anesthetic agents, was evaluated for its ability to produce topical anesthesia on the rabbit cornea, peripheral nerve block in the rat, and epidural anesthesia in the dog. High frequency and long duration of block can be attained if sufficiently high concentrations of STX are used, although latency is long and the doses used may produce systemic toxicity. Frequency of satisfactory blocks and mean duration of block can be increased and systemic toxicity reduced if STX is administered with a vasoconstrictor agent. Conventional local anesthetic agents also enhance the nerve blocking activity of STX. When appropriate concentrations of STX, vasoconstrictor and local anesthetic agents are used, systemic toxic effects are not manifested and the blocks produced exhibit the rapid onset and high frequency of block characteristic of the local anesthetic agent and the remarkably long duration of STX.

Anesthesia, Epidural↗

The local anesthetic activity of tetrodotoxin alone and in combination with vasoconstrictors and local anesthetics.

Tetrodotoxin (TTX), alone and in combination with various vasoconstrictors and local anesthetics, was evaluated for its ability to produce peripheral nerve blocks in the rat and central neural blocks in the cat and dog. High frequency and long duration of block can be attained if sufficiently high concentrations of TTX are used, although latency is long and high dosage may produce systemic toxicity. Frequency and mean duration of block can be increased and systemic toxicity reduced if TTX is administered with a vasoconstrictive agent. Conventional local anesthetics also enhance the nerve-blocking activity of TTX. When appropriate concentrations of TTX and local anesthetics are used, a high frequency of blocks characterized by short latency and long duration can be demonstrated. The studies present some indirect evidence that local anesthetics enhance TTX activity by reversibly increasing the permeability of various neural barriers to TTX.

Anesthesia, Epidural↗

Comparative study on anesthetic potency of dental local anesthetics assessed by the jaw-opening reflex in rabbits.

The potency of 4 local anesthetics to dental pulp was compared. Drugs were 4% articaine with 12 microgram/mL epinephrine (A12), 4% articaine with 6 microgram/mL epinephrine (A6), 2% lidocaine with 12.5 microgram/mL epinephrine (L), and 3% propitocaine with 0.03 IU/mL felypressin (P). Local anesthetics were injected into the dental root of the mandibular incisor. Electromyogram (EMG) of the digastric muscle was measured during the jaw-opening reflex induced by electrical stimulation. The disappearance of the EMG wave was judged as positive evidence of anesthesia. The determination of ED50 of the anesthetic was made by probit analysis. The ED50 of the A12 was minimal in all the tested anesthetics throughout the entire course. The potency in the A6 was 2.8 times that of the L. The potency of the A12 at the 15-minute measurement was 3.8 times that of the A6. The ED50 of the P was higher compared with those of the other 3 groups. It was concluded that articaine showed quicker onset than lidocaine and propitocaine and that there was a need to increase the dosage to attain a quick onset or to extend the duration.

Anesthetics, Local↗

Influence of anesthetic flow rate delivered by the Wand Local Anesthetic System on pain response to palatal injections.

PURPOSE: To compare pain response between two different flow rates (slow versus fast) of local anesthetic solution injected into palatal tissue using the recently available Wand Local Anesthetic System (WLAS), which provides the technologic advance to permit reliable replication of constant injection flow rates, regardless of tissue resistance. METHODS AND MATERIALS: Twenty adult subjects received bilateral palatal injections of local anesthetic in random sequence during the same appointment following topical anesthesia application. Pain response was measured by subjective self-report using a visual analogue scale, a quantified verbal descriptor scale, and a comparison to prior injection experience, as well as an operator's global assessment of the subject's pain response. Heart rate, as a physiologic indicator of pain response, was also recorded. RESULTS: All measurements of pain response were statistically less for the slow compared to the fast injection rate. No significant difference in mean heart rate, however, was demonstrated between the two flow rates. A slow, constant flow rate (161 sec/mL) of a 0.3 mL volume of local anesthetic solution was statistically less painful than a fast flow rate (29 sec/mL) during palatal injection. Contrary to the manufacturer's claim, the WLAS reduced but did not eliminate pain elicited by palatal injections in some patients.

Adult↗

[Comparison of the influence of different anesthetic protocols in the development of post-anesthetic arrhythmia in the dog].

Post-anesthetic holter monitoring was performed in 2 patient groups in order to compare the incidence of cardiac arrhythmias as a result of different anesthetic protocols. The 2 groups differed in their anesthetic protocol. Both groups received levomethadone as pre-anesthetic. The dogs in group A (n = 30) additionally received diazepam, the dogs in group B (n = 30) received propofol instead. Anesthesia was maintained by isoflurane in group A and a propofol constant rate infusion in group B. In each patient 2 holter monitorings were performed. The first recording began directly after anesthesia. As a comparison a second recording was performed on the 5th post-operative day. The recorded number of arrhythmias was low and no statistical difference was demonstrated between the 2 patient groups.

Anesthetics, Intravenous↗

Effect of local anesthetic concentration on the anesthetic level in digital transthecal block.

Transthecal digital block is an effective anesthesia. The purpose of this study was to analyze the effect of different anesthetic concentrations on the anesthetic level of transthecal block. From July 2003 to August 2003, 17 patients with trigger finger received local anesthesia by transthecal digital block. The patients were randomized to receive either 1 mL 1% lidocaine and 0.5 mL betamethasone (7 mg/mL), or 1 mL 2% lidocaine and 0.5 mL betamethasone. Anesthetic intensity was checked over different aspects of digits. The 2% lidocaine group showed significantly better pain scores over the dorsal aspect of the digits (p = 0.002). The most effective anesthesia was in the volar aspect of the digits. Anesthesia was least effective in the dorsum of the digit at the lower anesthetic dose.

Adult↗

Pollution of ambient air by volatile anesthetics: a comparison of 4 anesthetic management techniques.

Long-term exposure to waste anesthetic gas (WAG) may lead to health problems. The purpose of this study was to compare WAG concentrations resulting from 4 combinations of fresh gas flow (FGF) and vaporizer settings during a simulated intravenous induction in which the anesthetic is deepened using a volatile anesthetic delivered via mask ventilation before intubation. By using a lung model, WAG was sampled 3 times each using 4 combinations and 3 volatile anesthetics: 3% sevoflurane, 2% isoflurane, and 6% desflurane. The combinations were FGF off/vaporizer on, FGF on/vaporizer off, both on, and both off. WAG was measured using a MIRAN Ambient Air Analyzer placed at a level approximating the anesthetist's head. One-way analysis of variance with a Student-Newman-Keuls post hoc test was used to compare the concentration of WAG among the combinations of FGF/vaporizer settings for each agent. Regardless of the agent, only the FGF on/vaporizer on combination at 60 seconds resulted in a statistically greater WAG level (P < .005). The results support using 3 of the 4 combinations examined when mask ventilation with a volatile agent accompanies intravenous induction. Future studies should examine other methods of controlling WAG levels and use time-weighted averages to help address clinical significance.

Adult↗

Anesthetic and hemodynamic effects of the stereoisomers of medetomidine, an alpha 2-adrenergic agonist, in halothane-anesthetized dogs.

The anesthetic-sparing and hemodynamic effects of the stereoisomers of the highly selective alpha 2-adrenergic agonist medetomidine were studied in halothane-anesthetized dogs. Male beagles were anesthetized with halothane in oxygen. After a 2-hour equilibration period, halothane MAC and baseline hemodynamic functions were determined. DL-(n = 7), D- (n = 5), or L-medetomidine (n = 5) at 1, 3, and 10 micrograms/kg was administered via a right atrial port over 15 minutes while each dog was given halothane at the MAC dose for that animal. Twenty minutes after the end of infusion (when the hemodynamic variables were stable), hemodynamic function was reassessed. Halothane MAC was then redetermined. MAC for halothane significantly decreased after DL-medetomidine administration in a dose-dependent fashion to the extent that at the highest dose (10 micrograms/kg) the halothane MAC was less than 0.1%. This effect could be mimicked by the D-isomer, whereas the L-isomer was without effect. Neither isomer changed the mean arterial pressure, whereas only the D-isomer significantly decreased heart rate and cardiac output. Medetomidine, the highly selective alpha 2-adrenergic agonist, reduces the MAC for volatile anesthesia by a greater degree than with any other physiologic, pharmacologic, or pathologic intervention thus far reported. The fact that this effect is stereospecific suggests a structure activity relation that can be accounted for by a homogeneous receptor population. The role of medetomidine as a supplemental anesthetic agent appears promising and requires further investigation.

Adrenergic alpha-Agonists↗

Alkalinization of local anesthetics. Which block, which local anesthetic?

BACKGROUND AND OBJECTIVES: A number of clinical studies have been performed in an attempt to establish the effects of alkalinization on potency of local anesthetics. Conflicting results were obtained probably because different studies used different methods as well as different definitions of the effects. To determine the efficacy of alkalinization using different local anesthetic solutions and different regional blocks, 180 patients were studied in a randomized, double-blind fashion. The local anesthetic solutions studied were bupivacaine, mepivacaine, and lidocaine; the regional blocks studied were epidural block, axillary brachial plexus block, and femoral and sciatic nerve block. MATERIALS AND METHODS: In this study, 180 patients receiving epidural block (n = 60), sciatic and femoral nerve block (n = 60), and brachial plexus block (n = 60) were randomized to receive, in a double-blind fashion, a plain or a pH-adjusted solution of 2% mepivacaine, 2% lidocaine, or 0.5% bupivacaine. Onset of sensory analgesia, onset of maximum effect (peak effect or complete analgesia), duration of the block, onset, duration and density of motor block were evaluated using pinprick (Hollmen scale) and a 10-point decimal scale (Seow scale). RESULTS: concerning epidural block, the alkalinization of the local anesthetic shortened significantly the onset of sensory analgesia in the dermatome corresponding to the lumbar interspace used for epidural puncture (L3-L4) and increased the spread of the epidural block in all the groups. The onset of sensory analgesia at L4 level ranged from 10 minutes for plain bupivacaine to 3 minutes for alkalinized lidocaine, whereas the onset at T10 level ranged from 16 minutes for plain bupivacaine and mepivacaine to 12.3 minutes for alkalinized lidocaine. The effects of alkalinization were more evident with lidocaine and bupivacaine. Concerning femoral and sciatic nerve blocks, a statistically significant shorter onset of sensory analgesia and motor block were observed with mepivacaine. Concerning brachial plexus axillary block, the effects of alkalinization were more evident with lidocaine. CONCLUSIONS: Alkalinization produced the best results with lidocaine and bupivacaine for epidural block, with lidocaine for brachial plexus block, and with mepivacaine for sciatic and femoral nerve blocks.

Adult↗

Methods to produce calibration mixtures for anesthetic gas monitors and how to perform volumetric calculations on anesthetic gases.

A simple procedure for making calibration mixtures of oxygen and the anesthetic gases isoflurane, enflurane, and halothane is described. One to ten grams of the anesthetic substance is evaporated in a closed, 11,361-cc glass bottle filled with oxygen gas at atmospheric pressure. The carefully mixed gas is used to calibrate anesthetic gas monitors. By comparison of calculated and measured volumetric results it is shown that at atmospheric conditions the volumetric behavior of anesthetic gas mixtures can be described with reasonable accuracy using the ideal gas law. A procedure is described for calculating the deviation from ideal gas behavior in cases in which this is needed.

Anesthesia, Inhalation↗

The relationship between anesthetic potency (minimum alveolar concentration) and molecular shape; structural studies on conventional inhalational anesthetics.

We have explored the ability of molecular mechanics energy calculation as a probe to obtain quantitative information about the molecular shape and energies of inhalational anesthetics. (Molecular mechanics is a readily accessible, nonquantum mechanical method of computing detailed molecular structure from energetical viewpoint.) From this aspect, the structure-activity relationships of ten inhalational anesthetics were studied. Using this method, stable conformers of these anesthetics are deduced with various physicochemical parameters. The importance of dipole interaction as the major determinant of stable conformation was suggested, and reasonable correlations between anesthetic potency (minimum alveolar concentration: MAC) and components of dipole moments, with reference to the specific sites of molecules, were obtained. The results indicate that there are important polar components which play a major role in anesthesia.

Journal Article↗

The effect of anesthetic charge on anesthetic-phospholipid interactions.

Cationic and uncharged forms of a tertiary amine local anesthetic are reported to have different properties and potencies as nerve blocking agents. However, the relative capacities of each form of the local anesthetic to perturb the properties of different model membrane systems is unknown. For this reason we have studied the effects of uncharged lidocaine (high pH) and its quaternary amine analogue (W49091) on the phase transition properties of DMPS, DPPE and DPPC liposomes using high-sensitivity differential scanning calorimetry. We report that neutral lidocaine interacts similarly with all three phospholipids. This interaction results in a decrease in the temperature of the gel leads to liquid crystalline phase transition (Tm), an increase in the enthalpy of the transition (delta H), and a slight decrease in the cooperativity of melting. Quaternary lidocaine (W49091), on the other hand, interacts significantly with only DMPS; the result being again a decrease in the temperature of DMPS melting, an increase in delta H, and a slight decrease in the cooperativity of the phase transition. These results are interpreted to indicate that uncharged lidocaine enters the membrane during the DPPE and DPPC phase transitions. In the case of DMPS, an influx of both charged forms of lidocaine must occur at Tm. These anesthetic fluxes at the lipid's phase transition are suggested to be responsible for the observed elevated enthalpies of the respective transitions. The observation that the cationic form of lidocaine does not significantly modify the behavior of DPPC and DPPE liposomes suggests that these lipids are not important components of the anesthetic's site in nerve membranes. However, the dramatic perturbation of the properties of DMPS by W49091 suggests that phosphatidylserine may comprise part of this inhibitory site.

Calorimetry, Differential Scanning↗

Use of ion-exchange membranes to measure transfer free energies of charged local anesthetics: correlation to anesthetic potency.

Ion-selective electrodes, sensitive to local anesthetic cations, were prepared with carboxylated poly(vinyl chloride) (PVC) membranes. Three plasticizers with varying degrees of polarity were used to adjust the hydrophobicity of the membrane. The affinity of the drug to the ion-exchange membrane was measured by the electromotive force of the cation-selective electrodes. The difference in the transfer free energies of the anesthetics for the membrane was estimated in reference to dibucaine. The values correlated to their clinical potencies. By comparing drugs with similar structures, the transfer free energy per methylene moiety linked to the hydrophilic domain was found to be -1.7 kJ.mol-1, and that of Cl linked to the hydrophobic domain was -3.1 kJ.mol-1. Interferences from Na+ and K+ were estimated as the selectivity coefficients against dibucaine. The values were 2.6 x 10(-5) for Na+ and 1.2 x 10(-4) for K+. The ion-exchange membrane appears to mimic the surface properties of cell membranes. These cation-selective electrodes have potential applicability in measuring charged local anesthetic concentrations (activities) in biological materials under limited conditions.

Anesthetics↗

Pulmonary and systemic hemodynamic effects of delta9-tetrahydrocannabinol in conscious and morphine--chloralose-anesthetized dogs: anesthetic influence on drug action.

Pulmonary and systemic hemodynamic effects of delta 9-tetrahydrocannabinol (delta 9-THC) in conscious dogs and in those anesthetized with morphine (3 mg/kg, i.m.) plus alpha-chloralose (100 mg/kg i.v.) were evaluated in this study. A decrease in the heart rate, cardiac output (PBF) and a concomitant increase in the pulmonary arterial pressure (PAP), pulmonary vascular resistance (PVR) and right ventricular stroke work (RVSW) observed in conscious animals following the administration of delta 9-THC were qualitatively similar to the effects reported in dogs anesthetized with sodium pentobarbital; however, unlike in the pentobarbital group, hypotensive effects to THC were not evident in the consious animals. In contrast, the effect of delta 9-THC in morphine--chloralose dogs were different; in this group delta 9-THC administration resulted in increases in the heart rate the PBF, and significant reductions in PAR, PVR and RVSW. Further, a decrease in the arterial blood pressure noted following THC administration was closely associated with a reduction in the total peripheral resistance in the morphine--chloralose group. The results of this study indicated that the pulmonary effects of THC in dogs may be related to its actions on the heart rate and differ qualitatively as well as quantitatively depending on the anesthetic used.

Anesthetics↗