scholarly journals Opposing mechanisms underlying differential changes in brain oxygen and temperature induced by intravenous morphine

2018 ◽  
Vol 120 (5) ◽  
pp. 2513-2521 ◽  
Author(s):  
Ernesto Solis ◽  
Anum Afzal ◽  
Eugene A. Kiyatkin
Keyword(s):  
Respiratory Depression ◽  
Neurovascular Coupling ◽  
Oxygen Sensors ◽  
Blood Oxygen ◽  
Brain Hypoxia ◽  
Differential Effects ◽  
Oxygen Levels ◽  
Brain Oxygen ◽  
Intravenous Morphine ◽  
High Doses

Morphine remains widely used in clinical settings due to its potent analgesic properties. However, one of the gravest risks of all opioids is their ability to induce respiratory depression and subsequent brain hypoxia that can lead to coma and death. Due to these life-threatening effects, our goal was to examine the effects of intravenous morphine at a wide range of doses (0.1–6.4 mg/kg) on changes in brain oxygen levels in freely moving rats. We used oxygen sensors coupled with high-speed amperometry and conducted measurements in the nucleus accumbens (NAc) and subcutaneous (SC) space, the latter serving as a proxy for blood oxygen levels that depend on respiratory activity. We also examined the effects of morphine on NAc, muscle, and skin temperature. Morphine induced dose-dependent decreases in SC oxygen levels, suggesting respiratory depression, but differential effects on NAc oxygen: increases at low and moderate doses (0.1–1.6 mg/kg) and decreases at the highest dose tested (6.4 mg/kg). Morphine also increased brain temperature at low and moderate doses but induced a biphasic, down-up change at high doses. The oxygen increases appear to result from a neurovascular coupling mechanism via local vasodilation and enhanced oxygen entry into brain tissue to compensate for blood oxygen drops caused by modest respiratory depression. At high morphine doses, this adaptive mechanism is unable to compensate for the enhanced respiratory depression, resulting in brain hypoxia. Hence, morphine appears to be safe when used as an analgesic at clinically relevant doses but poses great risks at high doses, likely to be abused by drug users. NEW & NOTEWORTHY With the use of oxygen sensors coupled with amperometry, we show that morphine induces differential effects on brain oxygen levels, slightly increasing them at low doses and strongly decreasing them at high doses. In contrast, morphine dose dependently decreases oxygen levels in the SC space. Therefore, morphine engages opposing mechanisms affecting brain oxygen levels, enhancing them through neurovascular coupling at low, clinically relevant doses and decreasing them due to dramatic respiratory depression at high doses, likely to be abused.

Modulation of respiration during brain hypoxia

1990 ◽  
Vol 68 (2) ◽  
pp. 441-451 ◽  
Author(s):  
J. A. Neubauer ◽  
J. E. Melton ◽  
N. H. Edelman
Keyword(s):  
Animal Models ◽  
Respiratory Depression ◽  
Cellular Metabolism ◽  
Oxygen Availability ◽  
Cellular Systems ◽  
Respiratory Neuron ◽  
Brain Hypoxia ◽  
Cellular Basis ◽  
Neuronal Inhibition ◽  
Limited Oxygen

This review is a summary of the effects of brain hypoxia on respiration with a particular emphasis on those studies relevant to understanding the cellular basis of these effects. Special attention is given to mechanisms that may be responsible for the respiratory depression that appears to be the primary sequela of brain hypoxia in animal models. Although a variety of potential mechanisms for hypoxic respiratory depression are considered, emphasis is placed on changes in the neuromodulator constituency of the respiratory neuron microenvironment during hypoxia as the primary cause of this phenomenon. Hypoxia is accompanied by a net increase in neuronal inhibition due to both decreased excitatory and increased inhibitory neuromodulator levels. A survey of hypoxia-tolerant cellular systems and organisms suggests that hypoxic respiratory depression may be a manifestation of the depression of cellular metabolism, which appears to be a major adaptation to limited oxygen availability in these systems.

Respiratory and Circulatory Responses to Hypoxia in the Lobster Homarus Americanus

1975 ◽  
Vol 62 (3) ◽  
pp. 637-655 ◽  
Author(s):  
B. R. MCMAHON ◽  
J. L. WILKENS
Keyword(s):  
Oxygen Consumption ◽  
Oxygen Uptake ◽  
Homarus Americanus ◽  
Control Mechanisms ◽  
Blood Oxygen ◽  
Experimental Conditions ◽  
Oxygen Levels ◽  
Wide Range ◽  
Oxygen Tensions

Contrary to previous reports, oxygen consumption is maintained over a wide range of external oxygen tensions in the lobster Homarus americanus. In animals acclimated to the experimental conditions this response is mediated by increased branchial pumping, increased effectiveness of oxygen uptake by the gills and an increased contribution by the respiratory pigment to the oxygen delivered to the tissues. Circulatory blood oxygen levels are generally high in lobsters resting in well-aerated water. Mechanisms for detection of hypoxia and possible control mechanisms are discussed.

Limitations of potentiometric oxygen sensors operating at low oxygen levels

2011 ◽  
Vol 160 (1) ◽  
pp. 1159-1167 ◽  
Author(s):  
A. Lund ◽  
T. Jacobsen ◽  
K.V. Hansen ◽  
M. Mogensen
Keyword(s):  
Oxygen Sensors ◽  
Low Oxygen ◽  
Oxygen Levels

Very-low-dose ketamine for the management of pain and sedation in the ICU

2018 ◽  
Vol 4 (1) ◽  
pp. 54 ◽  
Author(s):  
Mario De Pinto, MD ◽  
Jill Jelacic, MD ◽  
William T. Edwards, PhD, MD
Keyword(s):  
Mechanical Ventilation ◽  
Case Report ◽  
Respiratory Depression ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Low Dose ◽  
Anesthetic Agent ◽  
Cardiovascular Instability ◽  
High Doses ◽  
Very High

Management of pain in critically ill patients can be very difficult. In the attempt to provide comfort with adequate levels of opioids and sedatives, respiratory depression and cardiovascular instability may become difficult to control in patients with labile hemodynamics and poor cardiopulmonary reserve. The use of medications like ketamine, an anesthetic agent that in subanesthetic doses has been reported to be effective in preventing opioidinduced tolerance and to have analgesic properties, may be of help, especially in patients who develop tolerance, leading to rapidly escalating doses of opioids and sedatives. The case report presented here shows how a very low dose of ketamine can be helpful for the management of pain and sedation in critically ill patients, especially when they are ready to be weaned from mechanical ventilation, and very high doses of opiods and sedatives do not permit it.

Clearance of Continuous Intravenous Morphine for Severe Cancer Pain

1987 ◽  
Vol 21 (12) ◽  
pp. 981-985
Author(s):  
Marc L. Citron ◽  
John R. Reynolds ◽  
Wen-Nuei Lin ◽  
Peter D. Frade ◽  
Mark Schemansky ◽  
...  
Keyword(s):  
Steady State ◽  
Cancer Pain ◽  
Cancer Patients ◽  
Intractable Pain ◽  
Time Period ◽  
Elimination Half ◽  
Steady State Serum ◽  
Intravenous Morphine ◽  
High Doses ◽  
Time Required

Four cancer patients with intractable pain received continuous morphine infusions in doses of 15–275 mg/h for a time period ranging from 4 to 27 days. Serum morphine concentrations were determined periodically following adjustments in infusion rates. As doses were changed and continued at static hourly rates, serum morphine concentrations were relatively constant 20 hours and beyond the time of the respective change, thus suggesting morphine elimination half-lives of ≤ 4 hours. High doses did not influence the time required to achieve steady-state concentrations. Steady serum morphine concentrations corresponded with hourly morphine doses in a parallel manner. High interpatient variabilities in clearances and steady-state serum morphine concentrations were noted. These data suggest that at morphine infusions up to 275 mg/h elimination pathways permit handling of increasing concentrations of morphine without nonlinear blood level increases. Also, marked interpatient and intrapatient variations in patient dose requirements were noted.

Patient Transport and Brain Oxygen in Comatose Patients

Neurosurgery ◽  
2010 ◽  
Vol 66 (5) ◽  
pp. 925-932 ◽  
Author(s):  
Edward W. Swanson ◽  
Justin Mascitelli ◽  
Michael Stiefel ◽  
Eileen MacMurtrie ◽  
Joshua Levine ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Intensive Care Unit ◽  
Intensive Care ◽  
Lung Function ◽  
Parameter Estimate ◽  
Brain Hypoxia ◽  
Average Decrease ◽  
Brain Oxygen ◽  
Before And After ◽  
Head Computed Tomography

Abstract OBJECTIVE Transport of critically ill intensive care unit patients may be hazardous. We examined whether brain oxygen (brain tissue oxygen partial pressure [PbtO2]) is influenced by transport to and from a follow-up head computed tomography (transport head computed tomography [tHCT]) scan. METHODS Forty-five patients (24 men, 21 women; Glasgow Coma Scale score ≤8; mean age, 47.3 ± 19.0 years) who had a traumatic brain injury (n = 26) or subarachnoid hemorrhage (n = 19) were retrospectively identified from a prospective observational cohort of PbtO2 monitoring in a neurosurgical intensive care unit at a university-based level I trauma center. PbtO2, intracranial pressure, and cerebral perfusion pressure were monitored continuously and compared during the 3 hours before and after 100 tHCT scans. RESULTS The mean PbtO2 before and after the tHCT scans for all 100 scans was 37.9 ± 19.8 mm Hg and 33.9 ± 17.2 mm Hg, respectively (P = .0001). A decrease in PbtO2 (>5%) occurred after 54 tHCTs (54%) and in 36 patients (80%). In instances in which a decrease occurred, the average decrease in mean, minimum, and maximum PbtO2 was 23.6%, 29%, and 18.1%, respectively. This decrease was greater when PbtO2 was compromised (<25 mm Hg) before tHCT. An episode of brain hypoxia (<15 mm Hg) was identified in the 3 hours before tHCT in 9 and after tHCT in 19 instances. On average, an episode of brain hypoxia was 46.6 ± 16.0 (standard error) minutes longer after tHCT than before tHCT (P = .008). Multivariate analysis suggests that changes in lung function (PaO2/fraction of inspired oxygen [FiO2] ratio) may account for the reduced PbtO2 after tHCT (parameter estimate 0.45, 95% confidence interval: 0.024–0.871; P = .04). CONCLUSION These data suggest that transport to and from the intensive care unit may adversely affect PbtO2. This deleterious effect is greater when PbtO2 is already compromised and may be associated with lung function.

Differential Effects of Morphine on Corneal-Responsive Neurons in Rostral Versus Caudal Regions of Spinal Trigeminal Nucleus in the Rat

1998 ◽  
Vol 79 (5) ◽  
pp. 2593-2602 ◽  
Author(s):  
Ian D. Meng ◽  
James W. Hu ◽  
David A. Bereiter
Keyword(s):  
Transition Region ◽  
Extracellular Recording ◽  
Spinal Trigeminal Nucleus ◽  
Trigeminal Nucleus ◽  
Differential Effects ◽  
Intravenous Morphine ◽  
Evoked Activity ◽  
Autonomic Reflex ◽  
Initial Processing ◽  
Neuronal Groups

Meng, Ian D., James W. Hu, and David A. Bereiter. Differential effects of morphine on corneal-responsive neurons in rostral versus caudal regions of spinal trigeminal nucleus in the rat. J. Neurophysiol. 79: 2593–2602, 1998. The initial processing of corneal sensory input in the rat occurs in two distinct regions of the spinal trigeminal nucleus, at the subnucleus interpolaris/caudalis transition (Vi/Vc) and in laminae I-II at the subnucleus caudalis/spinal cord transition (Vc/C1). Extracellular recording was used to compare the effects of morphine on the evoked activity of corneal-responsive neurons located in these two regions. Neurons also were characterized by cutaneous receptive field properties and parabrachial area (PBA) projection status. Electrical corneal stimulation-evoked activity of most (10/13) neurons at the Vi/Vc transition region was increased [146 ± 16% (mean ± SE) of control, P < 0.025] after systemic morphine and reduced after naloxone. None of the Vi/Vc corneal units were inhibited by morphine. By contrast, all corneal neurons recorded at the Vc/C1 transition region displayed a naloxone-reversible decrease (55 ± 10% of control, P < 0.001) in evoked activity after morphine. None of 13 Vi/Vc corneal units and 7 of 8 Vc/C1 corneal units tested projected to the PBA. To determine if the Vc/C1 transition acted as a relay for the effect of intravenous morphine on corneal stimulation-evoked activity of Vi/Vc units, morphine was applied topically to the dorsal brain stem surface overlying the Vc/C1 transition. Local microinjection of morphine at the Vc/C1 transition increased the evoked activity of 4 Vi/Vc neurons, inhibited that of 2 neurons, and did not affect the remaining 12 corneal neurons tested. In conclusion, the distinctive effects of morphine on Vi/Vc and Vc/C1 neurons support the hypothesis that these two neuronal groups contribute to different aspects of corneal sensory processing such as pain sensation, autonomic reflex responses, and recruitment of descending controls.

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