Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085383 (hypocapnia)
 1,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was carried out to evaluate the effects of perioperative indomethacin on intracranial pressure (ICP), cerebral blood flow (CBF), and cerebral metabolism. Twenty patients subjected to craniotomy for supratentorial cerebral tumors were anesthetized with thiopental, fentanyl, nitrous oxide, and isoflurane. A PaCO2 level averaging 4.8 kPa (median) was achieved. The patients were randomized to intravenous indomethacin 50 mg or placebo administrated after exposure of the dura. ICP was measured continuously subdurally with a 22-gauge canula connected to a transducer. CBF and the arteriovenous difference of oxygen (AVDO2) were measured twice, before and after indomethacin/placebo administration. A significant decrease in ICP from 6.5 to 1.5 mm Hg (median) was found after indomethacin administration. This decrease was caused by a significant decrease in CBF associated with a significant increase in AVDO2. Indomethacin did not affect the cerebral metabolic rate of oxygen, the arteriovenous difference of lactate, or the lactate/oxygen index, suggesting that indomethacin did not provoke global cerebral ischemia. In the indomethacin group, dura was sufficiently relaxed in eight of nine patients and dura was opened without the occurrence of cerebral swelling. In one patient, mannitol treatment was necessary to prevent dural tightness. In the placebo group, mannitol supplemented with hypocapnia was applied in five patients. These findings suggest that perioperative treatment with indomethacin is an excellent treatment of intracranial hypertension during normocapnic isoflurane anesthesia for craniotomy.
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PMID:Effects of perioperative indomethacin on intracranial pressure, cerebral blood flow, and cerebral metabolism in patients subjected to craniotomy for cerebral tumors. 888 23

The present study tests the hypothesis that cerebral ischemia induced by severe hypocapnia modifies the N-methyl-D-aspartate (NMDA) receptor/ion channel complex in the cerebral cortical cell membranes of newborn piglets. Studies were performed in six newborn piglets subjected to ischemic hypoxia induced by hyperventilation (PaCO2, 9-11 mmHg) for 1 h. Comparisons were made to a normoxic group on room air (n = 6). Following hyperventilation, phosphocreatine decreased 80%, but ATP remained unchanged. NMDA receptor activation was determined by measuring [3H]MK-801 binding at concentrations varying from 2.5 to 50 nM. Following hyperventilation, Bmax decreased 52% to 0.50 +/- 0.04 pmol/mg protein (P = 0.001); however, the Kd value was unchanged at 7.45 +/- 0.79 nM. Spermine and magnesium dependent activation of the NMDA receptor was determined in the hyperventilated and control groups. With spermine concentrations increasing from 2.5 to 50 microM the maximal spermine dependent activation in the normoxic group was 13.7 +/- 7.93% which occurred at a concentration of 3.75 +/- 1.37 microM. In the hyperventilated group maximal activation was 32.4 +/- 23.5% (P = 0.095) at 4.58 +/- 2.46 microM (P = ns). With magnesium concentrations increasing from 2.5 to 100 microM the maximal magnesium dependent activation in the normoxic group was 17.0 +/- 13.6% which occurred at a concentration of 22.5 +/- 6.12 microM. In the hyperventilated group maximal activation was 26.3 +/- 14.9% (P = ns) at 4.58 +/- 2.92 microM (P < 0.0001). These data show that with less severe tissue hypoxia, as evidenced by conservation of ATP, there is less modification of the NMDA receptors. Ischemia induced by hyperventilation leads to an increase in spermine activation of the NMDA receptor, and the NMDA receptor is much more sensitive to magnesium as evidenced by the maximal activation occurring at a significantly lower magnesium concentration. Ischemia induced by hyperventilation modifies the spermine, magnesium, and MK-801 binding sites of the NMDA receptor and may result in increased NMDA receptor mediated neurotoxicity in the newborn brain.
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PMID:Modification of the N-methyl-D-aspartate (NMDA) receptor in the brain of newborn piglets following hyperventilation induced ischemia. 893 73

Monitoring of brain tissue partial pressure of O2 (ti-pO2) is a promising new technique that allows early detection of impending cerebral ischemia in brain-injured patients. The purpose of this study was to investigate the effects of standard therapeutic interventions used in the treatment of intracranial hypertension in comatose patients on cerebral oxygenation. In the neurosurgical intensive care unit ti-pO2, arterial blood pressure, intracranial pressure (ICP), cerebral perfusion pressure (CPP) and jugular bulb oxygen saturation (SjvO2) were prospectively studied (0.1 Hz acquisition rate) in 23 comatose patients (21 with severe traumatic brain injury, 2 with intracerebral hematoma) during various treatment modalities: elevation of CPP with dopamine (n = 35), lowering of the head (n = 22), induced arterial hypocapnia (n = 13), mannitol infusion (n = 16), and decompressive craniotomy (n = 1). Ischemic episodes ('IE' = ti-pO2 < 10 mmHg for > 15 min) within the first week after the insult were always associated with unfavorable neurological outcome. Elevation of CPP from 32 +/- 2 to 67 +/- 4 mmHg significantly improved ti-pO2 by 62% (13 +/- 2 to 21 +/- 1 mmHg) and reduced ICP indicating intact cerebral autoregulation. Further raising CPP from 68 +/- 2 to 84 +/- 2 mmHg did not alter ti-pO2. Mannitol-induced ICP reduction from 23 +/- 1 to 16 +/- 2 mmHg did not affect ti-pO2, nor did lowering of the head from 30 degrees to 0 degree. Hyperventilation from an endtidal pCO2 of 29 +/- 3 to 21 +/- 3 mmHg normalized ICP and CPP, but significantly reduced ti-pO2 from 31 +/- 2 to 14 +/- 3 mmHg. Decompressive craniotomy in a 15-year old patient with refractory intracranial hypertension instantly restored ti-pO2. Based on the present data, our understanding of many interventions previously believed to improve brain oxygenation might have to be re-evaluated. A CPP > 60 mmHg emerges as the most important factor determining sufficient brain tissue pO2. Any intervention used to further elevate CPP does not improve ti-pO2, to the contrary, hyperventilation even bears the risk of inducing brain ischemia.
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PMID:Brain tissue pO2-monitoring in comatose patients: implications for therapy. 919 72

Twenty patients subjected to craniotomy for supratentorial cerebral tumours were anaesthetized with thiopental, fentanyl, nitrous oxide, and isoflurane. A PaCO2 level averaging 4.8 kPa was achieved. The patients were randomized to intravenous indomethacin 50 mg or placebo administrated after exposure of the dura. A significant decrease in intracranial pressure from 6.5 to 1.5 mmHg (medians) was found after indomethacin administration. This decrease was caused by a significant decrease in cerebral blood flow associated with a significant increase in the arterio-venous oxygen difference. Indomethacin did not affect cerebral oxygen uptake, arteriovenous difference in lactate or the lactate/oxygen index, suggesting that indomethacin did not provoke global cerebral ischaemia. In the indomethacin group, dura was sufficiently relaxed in eight of nine patients, and dura was opened without the occurrence of cerebral swelling. In the placebo group, mannitol supplemented with hypocapnia was applied in five patients. These findings suggest that perioperative treatment with indomethacin is an excellent treatment of intracranial hypertension during normocapnic isoflurane anaesthesia for craniotomy.
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PMID:[Effect of indomethacin on the intracranial pressure]. 922 82

Intracranial pressure depends on cerebral tissue volume, cerebrospinal fluid volume (CSFV) and cerebral blood volume (CBV). Physiologically, their sum is constant (Monro-Kelly equation) and ICP remains stable. When the blood brain barrier (BBB) is intact, the volume of cerebral tissue depends on the osmotic pressure gradient. When it is injured, water movements across the BBB depend on the hydrostatic pressure gradient. CBV depends essentially on cerebral blood flow (CBF), which is strongly regulated by cerebral vascular resistances. In experimental studies, a decrease in oncotic pressure does not increase cerebral oedema and intracranial hypertension (ICHT). On the other hand, plasma hypoosmolarity increases cerebral water content and therefore ICP, if the BBB is intact. If it is injured, neither hypoosmolarity nor hypooncotic pressure modify cerebral oedema. Therefore, all hypotonic solutes may aggravate cerebral oedema and are contra-indicated in case of ICHT. On the other hand, hypooncotic solutes do not modify ICP. The osmotic therapy is one of the most important therapeutic tools for acute ICHT. Mannitol remains the treatment of choice. It acts very quickly. An i.v. perfusion of 0.25 g.kg-1 is administered over 20 minutes when ICP increases. Hypertonic saline solutes act in the same way, however they are not more efficient than mannitol. CO2 is the strongest modulating factor of CBF. Hypocapnia, by inducing cerebral vasoconstriction, decreases CBF and CBV. Hyperventilation is an efficient and rapid means for decreasing ICP. However, it cannot be used systematically without an adapted monitoring, as hypocapnia may aggravate cerebral ischaemia. Hyperthermia is an aggravating factor for ICHT, whereas moderate hypothermia seems to be beneficial both for ICP and cerebral metabolism. Hyperglycaemia has no direct effect on cerebral volume, but it may aggravate ICHT by inducing cerebral lactic acidosis and cytotoxic oedemia. Therefore, infusion of glucose solutes is contra-indicated in the first 24 hours following head trauma and blood glucose concentration must be closely monitored and controlled during ICHT episodes.
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PMID:[The internal environment and intracranial hypertension]. 975 May 95

Hyperventilation (HV) is routinely used in the management of increased intracranial pressure (ICP) in severe head injury. However, this treatment continues to be controversial because it has been reported that long-lasting reduced cerebral blood flow (CBF) due to profound sustained hypocapnia may contribute to the development or deterioration of ischemic lesions. Our goal in this study was to analyze the effects of sustained hyperventilation on cerebral hemodynamics (CBF, ICP) and metabolism (arterio jugular differences of lactates = AVDL). CO2-reactivity and CBF was estimated using AVDO2 (arteriojugular differences of oxygen content). Global cerebral ischemia and increased anaerobic metabolism were considered according to AVDO2 and AVDL respectively. Thirty-three patients with severe and moderate head injury and increased ICP were included. Within 72 hours after accident, patients were hyperventilated for a period of 4 hours. During this time jugular oxygen saturation (SjO2), arterial oxygen saturation (SaO2), ICP, mean arterial blood pressure (MABP), AVDO2 and AVDL were recorded. In our study, most patients preserved CO2-reactivity (88.2%). In these cases HV was very effective in lowering ICP. Our findings showed that this reduction was due to a CBF decrease. According to basal AVDO2 twenty-five patients (75.7%) were considered as hyperemic and eight (24.2%) as not hyperemic. Global ischemia and increased anaerobic metabolism were detected in one case in the non-hyperemic group. According to AVDO2 and AVDL, no adverse effects were found during four hours of HV in hyperemic patients. Nevertheless, AVDO2 and AVDL are global measurements and might not detect regional ischemia surrounding focal lesions such as contusions and haematomas. We suggest that monitoring of AVDO2 or other haemometabolic variables should be mandatory when sustained HV is used in the management of head injury patients.
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PMID:Cerebral hemodynamic changes during sustained hypocapnia in severe head injury: can hyperventilation cause cerebral ischemia? 977 27

Chronic prophylactic hyperventilation therapy should be avoided during the first 5 days after severe TBI and particularly during the first 24 h. CBF measurements in patients with severe TBI demonstrate that blood flow early after injury is low and strongly suggest that in the first few hours after injury the absolute values approach those consistent with ischemia. These findings are corroborated by AVdO2 and SjO2 and brain tissue O2 measurements. Hyperventilation will reduce CBF values even further, but will not consistently cause a reduction of ICP and may cause loss of autoregulation. The cerebral vascular response to hypocapnia is reduced in those with the most severe injuries (subdural hematomas and diffuse contusions), and there is substantial local variability in perfusion. While the CBF level at which irreversible ischemia occurs has not been clearly established, ischemic cell change has been demonstrated in 90% of those who die following TBI, and there is PET evidence that such damage is likely to occur when CBF drops below 15-20 cc/100 g/min. A prospective randomized clinical trial has determined that outcomes are worse when TBI patients are treated with chronic prophylactic hyperventilation therapy. Within the standard, guideline, and options, specific paCO2 thresholds have been described that are different for each of the three parameters. These individual thresholds were selected based on the preponderance of literature supporting those thresholds in the contexts of the statements which included them. With the exception of the threshold included for the standard in this guideline, it is emphasized that the paCO2 threshold is not as important as the general concept of hyperventilation. The preponderance of the physiologic literature concludes that hyperventilation during the first few days following severe traumatic brain injury, whatever the threshold, is potentially deleterious in that it can promote cerebral ischemia.
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PMID:The Brain Trauma Foundation. The American Association of Neurological Surgeons. The Joint Section on Neurotrauma and Critical Care. Hyperventilation. 1093 94

Perioperative levels of jugular bulb oxyhaemoglobin saturation (Sj(O(2))) and lactate concentration (Lj), and postoperative duration of Sj(O(2))<50% were compared between patients undergoing coronary artery bypass grafting (CABG) (n=86), heart valve (n=14) and abdominal aortic (n=16) surgery. Radial artery and jugular bulb blood samples were aspirated after induction of anaesthesia, during re-warming on cardiopulmonary bypass (CPB) (36 degrees C), on arrival in the intensive care unit (ICU) and, subsequently, at 1, 2 and 6 h after ICU admission. Most patients having heart surgery were hypocapnic at 36 degrees C on CPB. Following CABG and heart valve surgery, many patients were hypocapnic whereas after abdominal aortic surgery, most were hypercapnic. During CPB and postoperatively, Sj(O(2)) and Lj were significantly correlated to Pa(CO(2)) and the arterial concentration of lactate (La) respectively (P<0.05). After correction for arterial carbon dioxide tension (Pa(CO(2))) and La, there were no significant changes in Sj(O(2)) or Lj on CPB. Postoperatively, having corrected for Pa(CO(2)), there were significant effects on Sj(O(2)) over all groups as a result of time from surgery (P<0.001) and its interaction with operation type (P<0.001). Following correction for La, there were no postoperative effects on Lj. No significant differences (P=0.2) in duration of Sj(O(2))<50% existed between patients undergoing CABG (1054 (82) min), abdominal aortic (893 (113) min) and heart valve (1073 (91) min) surgery. The lack of significant reciprocal effects on Lj combined with the frequency of hypocapnia and strong influence of Pa(CO(2))()on Sj(O(2)), suggest that Sj(O(2))<50% during CPB and after cardiac surgery represents hypoperfusion as a consequence of hypocapnia rather than cerebral ischaemia.
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PMID:Cerebral hypoperfusion in immediate postoperative period following coronary artery bypass grafting, heart valve, and abdominal aortic surgery. 1149 94

23% of all septic patients develop septic encephalopathy which is associated with an increased mortality rate. Symptoms such as agitation, confusion and disorientation ranging from stupor to coma often develop in early sepsis. Severe hypotension is significantly associated with the development of septic encephalopathy. Several other factors which may play a role are also discussed: effects of inflammatory mediators on the brain, inadequate cerebral perfusion pressure, blood-brain barrier derangements, disturbances of the cerebral microcirculation, cerebral ischemia e.g. due to hypocapnia,metabolic changes, altered amino acid levels, transmitter imbalances, liver insufficiency, multiple organ failure and infections of the CNS, respectively. Compared to patients with an isolated infection,patients in septic shock have increased levels of aromatic amino acids such as phenylalanine and tryptophan in the plasma and brain as well as decreased levels of branched chain amino acids. Patients who died had higher levels of aromatic amino acids than the survivors. The correlation between aromatic amino acids and the APACHE II score was significant. The tryptophan metabolite quinolinic acid which can be synthesized in activated macrophages could act as an excitatory transmitter on the N-methyl-D-aspartate (NMDA) -receptor. Observations from experimental models indicate that activated NMDA receptors activate the neuronal isoform of the NO-synthase and other calcium dependent enzymes. This releases free radicals which may damage the DNA and activate the nuclear enzyme Poly-ADP-ribose-synthetase (PARS), resulting in energy depletion and cell death. Sepsis is the main cause of metabolic encephalopathies in critically ill patients. The differential diagnoses include hepatic, renal,hypoxic-ischemic or cardiovascular encephalopathies as well as encephalopathies,metabolic disorders and organ dysfunctions of other origin. Therapeutic interventions are numerous,however, so far only investigated in few controlled studies. The primary therapeutic goal is to maintain an adequate perfusion pressure and to prevent hypoxia and hypocapnia. Although the infusion of branched chain amino acids is controversial, experimental investigations demonstrated improvements improvements in an animal model with septic encephalopathy. Further investigations with respect to glutamate receptor antagonists, new radical scavengers, NO- and PARS-inhibitors may show whether these substances are suitable for the prophylaxis or early therapy of septic encephalopathy.
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PMID:[Septic encephalopathy. Diagnosis und therapy]. 1275 14

Nimodipine is a calcium entry blocker that shows promise in the therapy for cerebral ischemia. This study was undertaken to examine the interaction of nimodipine with the use of hypocapnia to control cerebral blood volume by reduction in cerebral blood flow (CBF), as might be applicable to patients undergoing anesthesia for neurosurgical procedures. Male adult Sprague-Dawley rats were anesthetized with pentobarbital 50 mg/kg i.p. and were mechanically ventilated at either normocapnia (Paco2 35-40 mm Hg) or hypocapnia (Paco2 23-25 mm Hg). Animals were randomized into four experimental groups in a 2 x 2 factorial design, employing Paco2 level and drug group as between-group factors: vehicle plus normocapnia (group 1, n = 6), nimodipine plus normocapnia (group 2, n = 7), vehicle plus hypocapnia (group 3, n = 6), and nimodipine plus hypocapnia (group 4, n = 6). Nimodipine (1 mug/kg/min) or vehicle was administered i.v. for a period of 45 min. CBF was then measured using [C]iodoantipyrine autoradiography. Hypocapnia decreased global CBF (p <0.0001) and nimodipine increased CBF (p <0.05). Although nimodipine increased global CBF (p <0.05) during normocapnia (89 +/- 8 versus 61 +/- 4 ml/100 g/min), during hypocapnia there was no significant difference between nimodipine and vehicle (45 +/- 3 versus 40 +/- 2 ml/100 g/min). Hypocapnia decreased local CBF in all structures examined, whereas nimodipine increased local CBF in some, but not all structures. In this model, prior institution of hypocapnia prevented nimodipine-induced global CBF increases.
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PMID:Nimodipine does not increase cerebral blood flow during hypocapnia in the rat. 1581 65


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