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M A Helfaer

Publications and source records attributed to M A Helfaer.

34 records · Page 2Linked to original sources
PubMed1993

Head injury in children.

Head injuries in children are frequently preventable. These injuries are usually the result of bicycle or motor vehicle accidents, abuse, or gun shot wounds. Maintenance of airway, breathing, and circulation immediately after the initial event may protect against ongoing cerebral damage. Despite these best efforts, brain injury often worsens after the initial insult (so called secondary brain injury). The pathophysiology of head injury has been more clearly delineated as a result of clinical and basic science research. It is still impossible to accurately predict, at the time of presentation, who will have a good and who will have a bad outcome. The focus of initial treatment is based on a sound understanding of cerebral pathophysiology, which is reviewed in this article. Maintenance of adequate cerebral blood flow and metabolism can be monitored by intracranial pressure monitors, jugular bulb catheter data, as well as noninvasive blood flow measurements. In the future, more specific pharmacologic agents will be available to prevent the sequence of events leading to secondary brain injury. A multidisciplinary approach to the treatment of the patients throughout their hospital and posthospital course is described. The hope is that early intervention and aggressive treatment will lead to improved outcome for children suffering head injury.

Brain Injuries↗
PubMed1993

Polyethylene glycol-conjugated superoxide dismutase improves recovery of postischemic hypercapnic cerebral blood flow in piglets.

We tested the hypothesis that administering polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) either before global cerebral ischemia or at the time of reperfusion would alter recovery of cerebral blood flow (CBF; microspheres) response to alteration in arterial PCO2 in pentobarbital-anesthetized, mechanically ventilated piglets (1 to 2-wk old). CBF was measured at an arterial PCO2 of approximately 3.3, 5.3, and 8.7 kPa before and 2 h after ischemia (10 min aortic cross clamp). To determine the effect of preischemic versus postischemic treatment with PEG-SOD, each piglet received two i.v. drug injections of either 30,000 U PEG-SOD or an equal volume of PEG diluent in a randomized, blinded fashion before ischemia and just before reperfusion. Cerebral oxygen consumption and somatosensory evoked potentials were measured during reperfusion as an assessment of brain function. During reperfusion, no group demonstrated delayed hypoperfusion. Hypercapnic CBF was less during reperfusion (48 +/- 6 mL/min/100 g) compared with preischemia (69 +/- 10 mL/min/100 g) in PEG/PEG-treated piglets. However, hypercapnic CBF during reperfusion was not different from preischemic values with either preischemic or postischemic PEG-SOD treatment. Improved return of hypercapnic CBF in PEG-SOD-treated piglets was not attributable to improved postischemic cerebral oxygen consumption. Somatosensory evoked potential amplitude was decreased similarly during reperfusion (approximately 25% of preischemic values) in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Disposition and respiratory effects of intrathecal morphine in children.

BACKGROUND: The extent and duration of respiratory depression after opioid administration are poorly defined in infants and children. METHODS: The disposition and respiratory effects of intrathecal morphine were studied in ten patients (ages 4 months-15 yr) after repair of craniofacial defects. Morphine, 0.02 mg/kg, was administered intrathecally before the end of surgery. Postoperatively, we determined the minute ventilation (VE) in response to increasing partial pressure of end-tidal carbon dioxide (PETCO2) during carbon dioxide rebreathing. The slope (VE/PETCO2) and intercept (VE at PETCO2 60 mmHg, VE 60) of the carbon dioxide response curve were calculated at 6, 12, and 18 h after morphine administration. Cerebrospinal fluid (CSF) and blood were analyzed for morphine concentration by radioimmunoassay. RESULTS: Mean VE/PETCO2 decreased from a preoperative value of 35.1 +/- 3.7 to 16.3 +/- 2.8 ml.kg-1 x min-1 x mmHg-1 at 6 h after morphine, and remained depressed to 23.4 +/- 2.9 and 23.5 +/- 3.3 ml.kg-1 x min-1 x mmHg-1 at 12 h and 18 h, respectively, compared to preoperatively). The infants' (n = 3) VE/PETCO2 at 6 h were 21, 4, and 27 ml.kg-1 x min-1 x mmHg-1. Mean VE 60 decreased from 874 +/- 125 to 276 +/- 32 ml x kg-1 x min-1 at 6 h, but then recovered at 12 and 18 h to 491 +/- 68 and 567 +/- 82 ml.kg-1 x min-1, respectively. The infants' VE 60 at 6 h were 350, 142, and 245 ml.kg-1 x min-1. Mean CSF morphine concentration was 2,860 +/- 540 ng/ml at 6 h, and decreased to 640 +/- 220 and 220 +/- 150 ng/ml at 12 and 18 h, respectively. CONCLUSIONS: Intrathecal morphine, 0.02 mg/kg, depressed the ventilatory response to carbon dioxide for up to 18 h concomitant with increased CSF morphine concentrations. Infants (4-12 months of age) did not exhibit greater ventilatory depression than did children (2-15 yr of age).

Administration, Inhalation↗
PubMed1993

Histamine-2-receptor blockade does not affect hyperemia after cerebral ischemia in young swine.

OBJECTIVE: To determine whether histamine-2 (H2) receptor antagonists can blunt the increase in cerebral blood flow after cerebral ischemia. DESIGN: Prospective, randomized trial. SETTING: Animal laboratory. SUBJECTS: Piglets aged 1 to 2 wks. INTERVENTIONS: Three groups of piglets were anesthetized with pentobarbital, mechanically ventilated, and hemodynamically monitored. Each animal was randomized to receive one of three treatments 20 mins before ischemia: famotidine (0.6 mg/kg i.v.), cimetidine (5 mg/kg i.v.), or an equivalent volume of saline (3 mL). Ischemia was maintained for 15 mins by tightening ligatures around the brachiocephalic trunk and left subclavian arteries plus the induction of hemorrhagic hypotension (50 mm Hg). Reperfusion was initiated by the reinfusion of shed blood and removal of the ligatures. MEASUREMENTS AND MAIN RESULTS: The three groups were not different with regard to baseline arterial blood gases, cerebral perfusion pressure, microsphere-determined cerebral blood flow, or oxygen consumption (VO2). Ischemia (cerebral blood flow < 5 mL/min/100 g of tissue) was demonstrated in all brain regions for all groups during arterial ligation with hemorrhage-induced hypotension. Blood flow rates were increased compared with preischemic values in all regions at 7 mins of reperfusion. For example, mean forebrain blood flow rates increased from 36 +/- 3 to 95 +/- 14 (SEM) mL/min/100 g of tissue in the group receiving saline, from 36 +/- 3 to 102 +/- 9 mL/min/100 g of tissue in the group receiving famotidine, and from 31 +/- 4 to 119 +/- 26 mL/min/100 g in the group receiving cimetidine. Overall, the three groups did not differ in regard to blood flow rates and cerebral VO2 values during ischemia and at 30 mins of reperfusion. CONCLUSIONS: We demonstrated that famotidine or cimetidine as compared with saline did not affect the pattern or extent of hyperemia after ischemia. This finding does not support the hypothesis that a H2-receptor mechanism is necessary for postischemic hyperemia.

Animals↗
PubMed1992

Comparison of cerebral blood flow by radionuclide cerebral angiography and by microspheres in cats.

BACKGROUND: Radionuclide cerebral angiography is commonly used as an adjunct to the diagnosis of brain death. Despite its acceptance as a diagnostic tool, it is not clear whether the absence of cerebral blood flow by radionuclide cerebral angiography denotes a complete lack of cerebral blood flow. METHODS: To compare cerebral blood flow estimated by radionuclide cerebral angiography with cerebral blood flow measured by the radiolabeled microsphere technique, we systematically varied cerebral perfusion pressure (mean arterial BP minus intracranial pressure) in anesthetized cats by infusing artificial cerebral spinal fluid into the lateral ventricle to increase intracranial pressure. We measured cerebral blood flow with both techniques as cerebral perfusion pressure was decreased from its baseline of 111 +/- 10 mm Hg to 20, 10, 5, 0, and less than 0 mm Hg, causing a stepwise decrease in cerebral blood flow. RESULTS: We found a correlation by regression analysis (r2 = .47, p less than .05) between radionuclide cerebral angiography and microsphere measurements of cerebral blood flow, when both blood flow measurements were expressed as a percentage of baseline values. However, if 20% of baseline flow was assigned as a cut-off point for critically low cerebral blood flow (based on human studies), radionuclide cerebral angiography was only 33% sensitive to detect critically reduced cerebral blood flow and had a positive predictive accuracy (of low-flow interpretation) of only 60%. Radionuclide cerebral angiography was unable to demonstrate a complete lack of cerebral blood flow, even in two instances when cerebral blood flow by microspheres was less than 0.1% of baseline. CONCLUSIONS: We conclude that the ability of radionuclide cerebral angiography to quantify low cerebral blood flow is poor, and that this technique may not identify severely reduced cerebral blood flow.

Animals↗
PubMed1992

Hypercapnic blood flow reactivity not increased by alpha-blockade or cordotomy in piglets.

We tested the hypothesis that differential sympathetic innervation explains the attenuated cerebral blood flow (CBF) response to hypercapnia (hyper) in fore-brain (fb) compared with brain stem in 1- to 2-wk-old piglets. In pentobarbital sodium-anesthetized piglets, CBF (microspheres) was measured during hypocapnia, normocapnia (normo), and hypercapnia [arterial CO2 partial pressure (PaCO2) of 25, 40, and 65 mmHg, respectively] in random sequence. After pretreatment values were obtained, piglets were randomized to undergo sham treatment (n = 5), high cervical spinal cord transection (n = 6), or pharmacological alpha-adrenergic blockade (prazosin 1 mg/kg + yohimbine 1 mg/kg, n = 6). After each experimental treatment, CO2 reactivity was again measured. Before experimental manipulation, hypercapnic reactivity [(CBFhyper - CBFnormo)/(PaCO2hyper - PaCO2normo)] in brain stem was approximately three times greater than in forebrain (e.g., sham; 3.6 +/- 0.8 vs. 1.2 +/- 0.3 ml.min-1.100 g-1.mmHg-1). Hypercapnic reactivity in forebrain was not increased by cord transection (1.4 +/- 0.3 vs. 1.1 +/- 0.2 ml.min-1.100 g-1.mmHg-1) or alpha-blockade (1.6 +/- 0.6 vs. 1.2 +/- 0.4 ml.min-1.100 g-1.mmHg-1). Likewise, hypercapnic cerebral vascular resistance (CVR) was unchanged by experimental treatment (e.g., CVRfb; cord transection 1.1 +/- 0.1 vs. 1.0 +/- 0.1; alpha-blockade 1.1 +/- 0.2 vs. 1.0 +/- 0.1 mmHg.ml-1.min-1.100 g-1). Hypocapnic vasoconstriction, however, was attenuated by both cord transection and alpha-blockade in forebrain and brain stem. We conclude that physiological stimulation of the noradrenergic component of the sympathetic nervous system does not explain regional differences in CBF reactivity during hypercapnia in 1- to 2-wk-old piglets.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1992

Tirilazad mesylate does not improve early cerebral metabolic recovery following compression ischemia in dogs.

BACKGROUND AND PURPOSE: Tirilazad mesylate (U74006F) has been reported to improve recovery following cerebral ischemia. We conducted a randomized blinded study to determine if the drug would improve immediate metabolic recovery after complete cerebral compression ischemia. METHODS: Mongrel dogs were anesthetized with pentobarbital and fentanyl and treated with either vehicle (citrate buffer, n = 8) or tirilazad (1.5 mg/kg i.v. plus 0.18 mg/kg/hr, n = 8). Normothermic complete cerebral compression ischemia was produced for 12 minutes by lateral ventricular fluid infusion to raise intracranial pressure above systolic arterial pressure. Cerebral high-energy phosphate concentrations and intracellular pH were measured by phosphorus magnetic resonance spectroscopy. Cerebral blood flow was measured with radiolabeled microspheres, and oxygen consumption was calculated from sagittal sinus blood samples. Somatosensory evoked potentials were measured throughout the experiment. RESULTS: During ischemia, both groups demonstrated complete loss of high-energy phosphates and a fall in intracellular pH (vehicle, 5.76 +/- 0.23; tirilazad, 5.79 +/- 0.26; mean +/- SEM). At 180 minutes of reperfusion, there were no differences between groups in recovery of intracellular pH (vehicle, 6.89 +/- 0.07; tirilazad, 6.88 +/- 0.18), phosphocreatine concentration (vehicle, 89 +/- 16%; tirilazad, 94 +/- 24% of baseline value), oxygen consumption (vehicle, 2.6 +/- 0.2 ml/min/100 g; tirilazad, 1.8 +/- 0.5 ml/min/100 g), or somatosensory evoked potential amplitude (vehicle, 11 +/- 6%; tirilazad, 7 +/- 4% of baseline value). Forebrain blood flow fell below baseline levels at 180 minutes of reperfusion in the tirilazad-treated animals but not in the vehicle-treated dogs (vehicle, 28 +/- 4 ml/min/100 g; tirilazad, 18 +/- 5 ml/min/100 g). CONCLUSIONS: We conclude that tirilazad pretreatment does not improve immediate metabolic recovery 3 hours following 12 minutes of normothermic complete ischemia produced by cerebral compression.

Animals↗
PubMed1992

Evidence for free radical mechanisms of brain injury resulting from ischemia/reperfusion-induced events.

Free radicals have been implicated in the injury that occurs to brain tissue in response to ischemia and reperfusion insults. Confirmatory in vivo studies have been limited by the difficulty in measuring free radicals in brain tissue. This review discusses potential mechanisms for free radical production in brain tissue and the evidence supporting the therapeutic efficacy of free radical scavengers. Free radicals may be produced during ischemia/reperfusion as a result of multiple mechanisms involving normal regulatory systems of intra-/extracellular metabolism. For example, metabolism of free fatty acids by the cyclo-oxygenase pathway and adenine nucleotides by xanthine oxidase has been proposed to produce free radical adducts during reperfusion. Therapeutic strategies aimed at decreasing brain injury from free radical production include administration of free radical scavengers at the time of reperfusion. Pharmacologic interventions for protection from free radical injury in brain are hindered because of limited access to the site of free production.

Animals↗
PubMed1991

Age-related cerebrovascular reactivity to CO2 after cerebral ischemia in swine.

We tested the hypothesis that cerebral blood flow (CBF) reactivity to CO2 after global ischemia takes longer to recover in 1- to 2-wk-old piglets than in 6- to 10-mo-old pigs. All animals were sedated with ketamine and anesthetized with pentobarbital sodium. Cerebral ischemia was produced by sequentially tightening ligatures around the inferior vena cava and ascending aorta for 10 min. The microsphere-determined CBF response to hypercapnia (arterial PCO2 approximately 65 mmHg) was depressed at 60 min of reperfusion (9 +/- 6% of preischemia; means +/- SE) and remained depressed at 120 min (33 +/- 23% of preischemia, means +/- SE) in young pigs. In older pigs, the response was also depressed at 60 min of reperfusion (21 +/- 9% of preischemia) but was not depressed at 120 min. The pattern for recovery of hypercapnic reactivity was present in most brain regions except cerebellum, where CO2 reactivity returned to control in young animals by 120 min of reperfusion. The response to hypocapnia (arterial PCO2 approximately 25 mmHg) was also better preserved in older pigs. In older pigs recovery of CO2 reactivity during reperfusion paralleled recovery of cerebral O2 consumption over time. We conclude that older pigs have quicker return of CBF CO2 reactivity following transient global ischemia, which may be due to age-related differences in mechanisms of vascular reactivity.

Aging↗
PubMed1991

Polyethylene glycol-conjugated superoxide dismutase fails to blunt postischemic reactive hyperemia.

We tested the hypothesis that superoxide dismutase (SOD) conjugated with polyethylene glycol (PEG-SOD) would alter hyperemia following complete global cerebral ischemia. Thirty minutes before ischemia pentobarbital-anesthetized piglets were assigned to receive 3 ml of either PEG-SOD (10,000 U/ml; n = 10), an equivalent concentration of PEG (n = 10), or saline (n = 10) in a randomized and blinded manner. Cerebral ischemia was sustained for 10 min by cross-clamping the ascending aorta. Measurements of cerebral blood flow (radiolabeled microspheres) and oxygen consumption were made before ischemia and at 2, 4, 8, 12, and 15 min of reperfusion. Plasma SOD activity was higher in PEG-SOD-treated piglets (134 +/- 8 U/ml) than in PEG or saline-treated piglets (less than 5 U/ml). All groups and all brain regions demonstrated postischemic hyperemia. There were no differences in blood flow between groups at any time point in any region. At 2 min of reperfusion, blood flow to cerebrum rose from 31 +/- 4 to 88 +/- 9 ml.min-1.100 g-1 (saline), 44 +/- 6 to 102 +/- 17 ml.min-1.100 g-1 (PEG), and 31 +/- 3 to 83 +/- 16 ml.min-1.100 g-1 (PEG-SOD). During reperfusion cerebral oxygen consumption was not different from preischemic values in any group. In conclusion, we demonstrated that exogenously administered PEG-SOD raises serum SOD activity but does not alter the patterns of early cerebral blood flow or metabolic recovery after 10 min of complete global cerebral ischemia in piglets.

Animals↗
PubMed1991

Age-related differences in recovery of blood flow and metabolism after cerebral ischemia in swine.

We tested two hypotheses: 1) that cerebral blood flow, oxygen consumption, and evoked potentials recover to preischemic values at 120 minutes of reperfusion more completely in 1-2-week-old piglets than in 6-10-month-old pigs after complete ischemia; and 2) that recovery of cerebral blood flow, oxygen consumption, and electrical function in piglets and pigs at 120 minutes of reperfusion is better after incomplete than after complete ischemia. During 30 minutes of ischemia produced by intracranial pressure elevation, cerebral blood flow determined by the microspheres technique was decreased to 0-1 ml/min/100 g with complete ischemia, to 1-10 ml/min/100 g with severe incomplete ischemia, or to 10-20 ml/min/100 g with moderate incomplete ischemia. During reperfusion after complete ischemia, both piglets and pigs demonstrated hyperemia but delayed hypoperfusion occurred in more brain regions in pigs, oxygen consumption returned to preischemic values in piglets but not in pigs (70 +/- 10% of preischemic values), and evoked potentials recovered better in piglets than in pigs (24 +/- 4% and 9 +/- 4% of preischemic values, respectively). Both piglets and pigs had fewer brain areas with hyperemia and hypoperfusion and improved oxygen consumption and electrical function during recovery from incomplete than from complete ischemia. We speculate that piglets tolerate complete ischemia better than pigs because of decreased reperfusion injury and that both groups recover better from incomplete than complete ischemia because of improved substrate supply during ischemia.

Aging↗
PubMed1991

Polyethylene glycol-conjugated superoxide dismutase fails to augment brain superoxide dismutase activity in piglets.

We studied the effect of intravenously administered polyethylene glycol-conjugated superoxide dismutase (8,000 units/kg) on brain superoxide dismutase activity in 44 1-2-week-old piglets in the absence and presence of global cerebral ischemia and reperfusion. Four groups (n = 6 each) of piglets not exposed to ischemia were studied. Enzyme administration increased plasma superoxide dismutase activity from less than 5 to 142 +/- 8 units/ml (mean +/- SEM) without increasing brain activity (e.g., activities in the caudate were 7.9 +/- 0.5 and 8.1 +/- 0.4 units/mg protein) for up to 2 hours following administration. Four additional groups (n = 5 each) of piglets were given either enzyme or polyethylene glycol 5 minutes prior to 10 minutes of global cerebral ischemia induced by aortic cross-clamping followed by either 5 or 45 minutes of reperfusion. Enzyme administration increased plasma superoxide dismutase activity from less than 5 to 144 +/- 5 units/ml but failed to increase brain activity even after 45 minutes of reperfusion (e.g., activities in the caudate were 8.5 +/- 0.3 and 8.6 +/- 0.6 units/mg protein). We conclude that intravenous polyethylene glycol-conjugated superoxide dismutase does not increase superoxide dismutase activity in the brain despite global ischemia and reperfusion.

Animals↗
PubMed1990

Age-related cerebrovascular response to global ischemia in pigs.

We tested the hypothesis that 1- to 2-wk-old pigs (piglet) have improved recovery of cerebral blood flow (CBF), cerebral oxygen consumption (CMRO2), and somatosensory-evoked potentials (SEP) compared with 6- to 8-mo-old pigs (pig) after transient global cerebral ischemia. All animals were anesthetized with pentobarbital sodium. After tracheostomy ventilation was adjusted to maintain normoxia (arterial oxygen pressure, 100-150 mmHg) and normocarbia (arterial carbon dioxide pressure, 35-40 mmHg). Arterial blood gases, blood pressure, and hemoglobin concentration remained within physiological limits throughout the experiment. Cerebral ischemia was produced by sequentially tightening ligatures around the inferior vena cava and ascending aorta. During ischemia the electroencephalogram and SEP became isoelectric within 40 and 120 s, respectively. At 10 min of reperfusion hyperemia occurred in most brain regions (e.g., whole brain: piglet, 270 +/- 45%; pig, 316 +/- 48%). In pigs delayed hypoperfusion occurred in all regions except white matter. In contrast, piglets only had delayed hyperperfusion to the brain stem and caudate nucleus. Throughout reperfusion CMRO2 was decreased in pigs (3.3 +/- 0.4 to 1.9 +/- 0.2 ml.min-1.100 g-1) but was not different from control (2.7 +/- 0.3 ml.min-1.100 g-1) in piglets. By the end of reperfusion SEP amplitude was closer to control in piglets than pigs (55 +/- 9 vs. 32 +/- 4% of control). We conclude that 1- to 2-wk-old piglets have quicker return of CBF, CMRO2, and SEP to control values after global ischemia, which mechanistically may explain previous reports of improved neurological recovery in young animals after transient ischemia.

Aging↗
PubMed1990

Anesthetic modulation of cerebral hemodynamic and evoked responses to transient middle cerebral artery occlusion in cats.

We measured cerebral blood flow and somatosensory evoked potentials during transient focal cerebral ischemia in cats to compare the effects of four commonly used anesthetic regimens: ketamine/fentanyl/N2O (fentanyl), pentobarbital, ketamine/alpha-chloralose (alpha-chloralose), and ketamine/halothane/N2O (halothane). Six cats in each group were subjected to 60 minutes of left middle cerebral artery occlusion followed by 120 minutes of reperfusion. Although the amplitude of the initial somatosensory evoked potential wave complex was highest in the alpha-chloralose group (58.6 +/- 16.5 microV) and smallest in the halothane group (27.5 +/- 5.7 microV), amplitude fell by 75% in all groups upon occlusion. Baseline cerebral blood flow varied substantially between groups (e.g., in the right intersylvian gyrus: fentanyl, 96 +/- 12; pentobarbital, 30 +/- 5; alpha-chloralose, 24 +/- 3; and halothane, 76 +/- 11 ml/min/100 g). Occlusion decreased cerebral blood flow to subcortical (e.g., left caudate) structures in all groups (fentanyl, 29 +/- 11%; pentobabital, 45 +/- 12%; alpha-chloralose, 27 +/- 13%; and halothane, 18 +/- 5% of baseline). Postischemic hyperemia occurred in the cortical regions of cats anesthetized with pentobarbital or alpha-chloralose that had reduced cerebral blood flows during occlusion but not in cats anesthetized with fentanyl (cerebral blood flow during occlusion not different from that of cats anesthetized with pentobarbital or alpha-chloralose) or halothane. After 120 minutes of reperfusion, cerebral blood flow had returned to baseline values in all groups. Recovery of cerebral blood flow and somatosensory evoked potential amplitude at that time did not differ among groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics↗
PubMedDate not supplied

Recurrent seizures in a neonate after lidocaine administration.

OBJECTIVE: We report recurrent seizures in a neonate after intravenous lidocaine administration at the recommended dose for intubation and supplementation of general anesthesia. STUDY DESIGN: Further evaluation of this case included determination of serum lidocaine level, serum electrolyte levels, and arterial blood gas values; cerebral spinal fluid analysis; an electroencephalogram; head ultrasonography; brain stem auditory evoked response testing; and a complete developmental evaluation. Previously published literature discussing lidocaine toxicity and pharmacokinetics is reviewed. RESULTS: The lidocaine level in the patient was 0.3 mg/L 2 hours after the last dose was administered. Results of the remaining studies were within normal limits, and the patient had no additional seizures several months after birth. CONCLUSION: We caution that lidocaine administration to newborn infants at previously accepted doses may result in life-threatening side effects, including prolonged seizures.

Anesthetics, Local↗