Phase I Safety Assessment of Intrathecal Neostigmine Methylsulfate in Humans 

1995 ◽  
Vol 82 (2) ◽  
pp. 331-343 ◽  
Author(s):  
David D. Hood ◽  
James C. Eisenach ◽  
Robin Tuttle
Keyword(s):  
Carbon Dioxide ◽  
Blood Pressure ◽  
Heart Rate ◽  
Side Effects ◽  
Healthy Volunteers ◽  
Nausea And Vomiting ◽  
Severe Nausea ◽  
End Tidal Carbon Dioxide ◽  
End Tidal ◽  
Ice Water

Background In dogs, sheep, and rats, spinal neostigmine produces analgesia alone and enhances analgesia from alpha 2-adrenergic agonists. This study assesses side effects and analgesia from intrathecal neostigmine in healthy volunteers. Methods After institutional review board approval and informed consent, 28 healthy volunteers were studied. The first 14 volunteers received neostigmine (50-750 micrograms) through a #19.5 spinal needle followed by insertion of a spinal catheter. The remaining 14 volunteers received neostigmine through a #25 or #27 spinal needle without a catheter. Safety measurements included blood pressure, heart rate, oxyhemoglobin saturation, end-tidal carbon dioxide, neurologic evaluation, and computer tests of vigilance and memory. Analgesia in response to ice water immersion was measured. Results Neostigmine (50 micrograms) through the #19.5 needle did not affect any measured variable. Neostigmine (150 micrograms) caused mild nausea, and 500-750 micrograms caused severe nausea and vomiting. Neostigmine (150-750 micrograms) produced subjective leg weakness, decreased deep tendon reflexes, and sedation. The 750-micrograms dose was associated with anxiety, increased blood pressure and heart rate, and decreased end-tidal carbon dioxide. Neostigmine (100-200 micrograms) in saline, injected through a #25 or #27 needle, caused protracted, severe nausea, and vomiting. This did not occur when dextrose was added to neostigmine. Neostigmine by either method of administration reduced visual analog pain scores to immersion of the foot in ice water. Conclusions The incidence and severity of these adverse events from intrathecal neostigmine appears to be affected by dose, method of administration, and baricity of solution. These effects in humans are consistent with studies in animals. Because no unexpected or dangerous side effects occurred, cautious examination of intrathecal neostigmine alone and in combination with other agents for analgesia is warranted.

scholarly journals Incidence of Artifacts and Deviating Values in Research Data Obtained from an Anesthesia Information Management System in Children

2018 ◽  
Vol 128 (2) ◽  
pp. 293-304 ◽  
Author(s):  
Anne-lee J. Hoorweg ◽  
Wietze Pasma ◽  
Leo van Wolfswinkel ◽  
Jurgen C. de Graaff
Keyword(s):  
Carbon Dioxide ◽  
Blood Pressure ◽  
Heart Rate ◽  
Oxygen Saturation ◽  
Information Management ◽  
Information Management System ◽  
Noninvasive Blood Pressure ◽  
Invasive Blood Pressure ◽  
End Tidal Carbon Dioxide ◽  
End Tidal

Abstract Background Vital parameter data collected in anesthesia information management systems are often used for clinical research. The validity of this type of research is dependent on the number of artifacts. Methods In this prospective observational cohort study, the incidence of artifacts in anesthesia information management system data was investigated in children undergoing anesthesia for noncardiac procedures. Secondary outcomes included the incidence of artifacts among deviating and nondeviating values, among the anesthesia phases, and among different anesthetic techniques. Results We included 136 anesthetics representing 10,236 min of anesthesia time. The incidence of artifacts was 0.5% for heart rate (95% CI: 0.4 to 0.7%), 1.3% for oxygen saturation (1.1 to 1.5%), 7.5% for end-tidal carbon dioxide (6.9 to 8.0%), 5.0% for noninvasive blood pressure (4.0 to 6.0%), and 7.3% for invasive blood pressure (5.9 to 8.8%). The incidence of artifacts among deviating values was 3.1% for heart rate (2.1 to 4.4%), 10.8% for oxygen saturation (7.6 to 14.8%), 14.1% for end-tidal carbon dioxide (13.0 to 15.2%), 14.4% for noninvasive blood pressure (10.3 to 19.4%), and 38.4% for invasive blood pressure (30.3 to 47.1%). Conclusions Not all values in anesthesia information management systems are valid. The incidence of artifacts stored in the present pediatric anesthesia practice was low for heart rate and oxygen saturation, whereas noninvasive and invasive blood pressure and end-tidal carbon dioxide had higher artifact incidences. Deviating values are more often artifacts than values in a normal range, and artifacts are associated with the phase of anesthesia and anesthetic technique. Development of (automatic) data validation systems or solutions to deal with artifacts in data is warranted.

Phase I Safety Assessment of Intrathecal Injection of an American Formulation of Adenosine in Humans

2002 ◽  
Vol 96 (1) ◽  
pp. 24-28 ◽  
Author(s):  
James C. Eisenach ◽  
David D. Hood ◽  
Regina Curry
Keyword(s):  
Carbon Dioxide ◽  
Blood Pressure ◽  
Heart Rate ◽  
Phase I ◽  
Controlled Trial ◽  
Intrathecal Injection ◽  
Open Label ◽  
Double Blind ◽  
End Tidal Carbon Dioxide ◽  
End Tidal

Background Preclinical studies of intrathecal adenosine suggest it may be effective in the treatment of acute and chronic pain in humans. A phase I safety trial of the intrathecal injection of a mannitol-containing formulation of adenosine in Sweden showed a considerable incidence of backache. We performed a phase I safety trial of intrathecal injection of the American formulation of adenosine, which lacks mannitol. Methods Following US Food and Drug Administration and institutional review board approval and written informed consent, 65 volunteers were studied in two trials: an open-label, dose-escalating trial with intrathecal adenosine doses of 0.25-2.0 mg (25 subjects) and a double-blind, placebo-controlled trial of adenosine, 2 mg (40 subjects). Blood pressure, heart rate, end-tidal carbon dioxide, and sensory, motor, and reflex neurologic functions were systematically examined for 24 h after injection, and volunteers were contacted by telephone at times up to 6 months after injection. Results Intrathecal adenosine did not affect blood pressure, heart rate, end-tidal carbon dioxide, or neurologic function. Headache was reported by 10 and back pain was reported by 8 of 30 subjects exposed to adenosine in the second double-blind trial, whereas none of these symptoms was reported by the 10 saline-treated subjects. Conclusion These data support further investigation of intrathecal adenosine for analgesia in humans and suggest that this agent does not produce a high incidence of severe side effects.

scholarly journals Cardiorespiratory variables, bispectral index and recovery of anesthesia in dogs anesthetized with isoflurane, treated or not with tramadol

2008 ◽  
Vol 60 (3) ◽  
pp. 613-619 ◽  
Author(s):  
P.A. Borges ◽  
N. Nunes ◽  
V.F. Barbosa ◽  
E.D.V. Conceição ◽  
C.T.D. Nishimori ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Heart Rate ◽  
Bispectral Index ◽  
Recovery Time ◽  
Saline Solution ◽  
Control Group ◽  
End Tidal Carbon Dioxide ◽  
Index Changes ◽  
End Tidal

It was studied fortuitous cardiorespiratory and bispectral index changes in dogs anesthetized with isoflurane associated or not to tramadol. Sixteen dogswere distributed in two groups named CG (control group) and TG (tramadol group). General anesthesia was induced in all animals with isoflurane via mask. After 10 minutes, the animals of CG received 0.05ml/kg of saline solution at 0.9%, and TG received 2mg/kg of tramadol, both via intramuscular. It was evaluated heart rate, systolic, diastolic and mean arterial pressures; electrocardiography; respiratory rate; oxihemoglobin saturation; end tidal carbon dioxide; bispectral index and recovery of anesthesia. The administration of tramadol in dogs anesthetized with isoflurane did not produce changes in cardiorespiratory variables, bispectral index and anesthetic recovery time. In addition, this association promoted good quality of anesthetic recovery.

scholarly journals Cerebral Blood Flow and Cognitive Performance in Postural Tachycardia Syndrome: Insights from Sustained Cognitive Stress Test

2020 ◽  
Vol 9 (24) ◽  
Author(s):  
Rachel Wells ◽  
Varun Malik ◽  
Anthony G. Brooks ◽  
Dominik Linz ◽  
Adrian D. Elliott ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Blood Pressure ◽  
Blood Flow ◽  
Stress Test ◽  
Orthostatic Stress ◽  
Postural Tachycardia Syndrome ◽  
Cognitive Stress ◽  
Postural Tachycardia ◽  
End Tidal Carbon Dioxide ◽  
End Tidal

Background The physiology underlying "brain fog" in the absence of orthostatic stress in postural tachycardia syndrome (POTS) remains poorly understood. Methods and Results We evaluated cognitive and hemodynamic responses (cardiovascular and cerebral: heart rate, blood pressure, end‐tidal carbon dioxide, and cerebral blood flow velocity (CBFv) in the middle cerebral artery at baseline, after initial cognitive testing, and after (30‐minutes duration) prolonged cognitive stress test (PCST) whilst seated; as well as after 5‐minute standing in consecutively enrolled participants with POTS (n=22) and healthy controls (n=18). Symptom severity was quantified with orthostatic hypotensive questionnaire at baseline and end of study. Subjects in POTS and control groups were frequency age‐ and sex‐matched (29±11 versus 28±13 years; 86 versus 72% women, respectively; both P ≥0.4). The CBFv decreased in both groups (condition, P =0.04) following PCST, but a greater reduction in CBFv was observed in the POTS versus control group (−7.8% versus −1.8%; interaction, P =0.038). Notably, the reduced CBFv following PCST in the POTS group was similar to that seen during orthostatic stress (60.0±14.9 versus 60.4±14.8 cm/s). Further, PCST resulted in greater slowing in psychomotor speed (6.1% versus 1.4%, interaction, P =0.027) and a greater increase in symptom scores at study completion (interaction, P <0.001) in the patients with POTS, including increased difficulty with concentration. All other physiologic responses (blood pressure and end‐tidal carbon dioxide) did not differ between groups after PCST (all P >0.05). Conclusions Reduced CBFv and cognitive dysfunction were evident in patients with POTS following prolonged cognitive stress even in the absence of orthostatic stress.

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