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Peter Reinstrup

Publications and source records attributed to Peter Reinstrup.

11 recordsLinked to original sources

Increased lactate levels impair the coagulation system--a potential contributing factor to progressive hemorrhage after traumatic brain injury.

Progressive intracerebral contusions are a major problem in the management of patients with severe traumatic brain injury that is also linked to worse outcome. Microdialysis studies have revealed that lactate levels are very high inside contusions, corresponding to significant acidosis. The current study was performed in an effort to investigate whether the lactate accumulation inside cerebral contusions may be a contributing factor to the prolonged bleeding inside contusions. We have investigated the effects of lactic acidosis on the coagulation system with rotational thromboelastometry. It was a laboratory study involving 6 healthy volunteers. Blood was drawn and the pH was adjusted by addition of lactic acid in vitro. The pH levels studied were 7.4, 7.2, 7.0, and 6.8. The pH was also readjusted to 7.4 by addition the buffer THAM to blood initially adjusted to a pH of 6.8 to study the reversibility of potential adverse effects induced by the lactic acidosis. We found the coagulation to be significantly impaired by lactic acidosis (P = 0.000l). The impairment found was reversible after correction of the acidosis by a buffer. In conclusion, we found that lactic acidosis impaired the coagulation system. The impairment caused by lactic acidosis may be one factor causing the progressive hemorrhage in posttraumatic cerebral contusions, known to have high levels of lactate and correspondingly low pH. It may also be important to consider in bleeding trauma patients.

Acidosis↗

Acidosis impairs the coagulation: A thromboelastographic study.

BACKGROUND: Coagulopathy is a contributor to and predictor of death in bleeding patients. Acidosis is known to be a predictor of worse outcome in trauma patients and to be a coexisting factor in coagulopathic patients, but it has not been studied if it is a causal factor in the development of coagulopathy. METHODS: We have adjusted the pH level in blood samples from healthy volunteers to different levels between 7.4 and 6.8 by the use of hydrochloric acid. Thereafter we have studied the coagulation at the different pH levels by the use of thromboelastography. RESULTS: We found a strong correlation between pH levels and impairment of the coagulation, where the clot strength is increased much slower at pH levels below 7.4 even though the initiation of the clotting seems to be normal. The clot formation time was increased by 168% at pH 6.8 as compared with pH 7.4 (p < 0.00001, r = 0.89) whereas the clotting time was left unaffected. CONCLUSIONS: Acidosis causes a strong impairment of the coagulation as measured with thromboelastography. The impairment found when lowering pH from 7.4 to 7.15 was almost identical to the impairment seen in another study by Kettner et al. when the temperature was lowered from 36 degrees C to 32 degrees C.

Acidosis↗

Ethanol impairs coagulation and fibrinolysis in whole blood: a study performed with rotational thromboelastometry.

The objective was to study the effects of ethanol on coagulation and fibrinolysis in whole blood. Blood samples from healthy volunteers were analyzed before and after in-vitro addition of ethanol in order to achieve ethanol concentrations of 0, 1, 2 and 4 per thousand, respectively (0, 22, 44 and 88 mmol/l). Coagulation and fibrinolysis were then assessed using rotational thromboelastometry. We found that increasing ethanol levels increasingly impaired coagulation as evaluated with rotational thromboelastometry, with a maximum prolongation of the clot formation time of 118% at an ethanol level of 4 per thousand (P < 0.000001). We also found a very strong impairment of fibrinolysis already at an ethanol level of 1 per thousand. This is the first study assessing the effects of ethanol on coagulation and fibrinolysis in a whole blood model. The impairment of coagulation is similar in nature to the impairment found in patients suffering from hypothermia. The impairment is at a level that may be of clinical importance (e.g. in patients suffering from trauma). The inhibition of fibrinolysis is obvious already at an ethanol level of 1 per thousand and it may be a contributing factor to the increased amount of coronary and cerebrovascular ischemic events after binge drinking.

Alcohol Drinking↗

Postoperative continuous intrathecal pain treatment in children after selective dorsal rhizotomy with bupivacaine and two different morphine doses.

BACKGROUND: Children undergoing selective dorsal rhizotomy (SDR) experience severe pain postoperatively; a pain related to both the extensive surgical exposure with multilevel laminectomy and nerve root manipulation. We sought to define an optimal dose of continuous intrathecal (IT) morphine and bupivacaine to treat this severe pain. The aim of this study was to compare two different concentrations of morphine in a fixed dose of bupivacaine with regard to the analgesic effect and survey if they differed in side effects. METHODS: Twenty-six children, aged 2.7-7.4 years undergoing SDR were included in this study. Postoperatively 11 children received a continuous infusion of morphine 0.4 microg x kg(-1) x h(-1) and bupivacaine 40 microg x kg(-1) x h(-1) (low-dose group) and 15, a continuous infusion of morphine 0.6 microg x kg(-1) x h(-1) and bupivacaine 40 microg x kg(-1) x h(-1) (high-dose group). The Behavioral Observational Pain Scale (BOPS) was used to evaluate pain. RESULTS: Better pain relief was obtained in the high-dose group seen in lower BOPS score compared with the low-dose group [P = 0.03, Fisher's permutation test and P = 0.06 Wilcoxon-Mann-Whitney (WMW) test]. The low-dose group received seven times as much ketobemidone 0.43 +/- 0.54 mg x kg(-1) 48 h(-1) compared with 0.06 +/- 0.09 mg x kg(-1) 48 h(-1) in the high-dose group (P = 0.0005 Fisher's permutation test, P = 0.0017 WMW test). There was no statistical difference in pruritus and postoperative nausea and vomiting between the groups. Respiratory and hemodynamic depression was not found. CONCLUSION: This study shows that, compared with low-dose, the higher dose of continuous IT morphine combined with bupivacaine, significantly reduce pain score and postoperative intravenous analgesic requirements without increasing adverse effects.

Analgesics, Opioid↗

An in vitro evaluation of standard rotational thromboelastography in monitoring of effects of recombinant factor VIIa on coagulopathy induced by hydroxy ethyl starch.

BACKGROUND: Rotational thromboelastography (ROTEG) has been proposed as a monitoring tool that can be used to monitor treatment of hemophilia with recombinant factor VIIa (rFVIIa). In these studies special non-standard reagents were used as activators of the coagulation. The aim of this study was to evaluate if standard ROTEG analysis could be used for monitoring of effects of recombinant factor VIIa (rFVIIa) on Hydroxy Ethyl Starch-induced dilutional coagulopathy. METHODS: The study was performed in vitro on healthy volunteers. Prothrombin time (PT) and ROTEG analysis were performed after dilution with 33% hydroxy ethyl starch and also after addition of rFVIIa to the diluted blood. RESULTS: PT was impaired with INR changing from 0.9 before dilution to 1.2 after dilution while addition of rFVIIa to diluted blood lead to an overcorrection of the PT to an International Normalized Ratio (INR) value of 0.6 (p = 0.01). ROTEG activated with the contact activator ellagic acid was impaired by hemodilution (p = 0.01) while addition of rFVIIa had no further effects. ROTEG activated with tissue factor (TF) was also impaired by hemodilution (p = 0.01) while addition of rFVIIa lead to further impairment of the coagulation (p = 0.01). CONCLUSIONS: The parameters affected in the ROTEG analysis were Clot Formation Time and Amplitude after 15 minutes while the Clotting Time was unaffected. We believe these effects to be due to methodological problems when using standard activators of the coagulation in the ROTEG analysis in combination with rFVIIa.

Journal Article↗

Thrombocytopenia predicts progressive hemorrhage after head trauma.

Patients with traumatic brain injury (TBI) often show progression of hemorrhagic injuries (PHI) after admission to the hospital. This progression is correlated with poor outcome. In this study, we have investigated if thrombocytopenia was a risk factor for PHI. The study was performed on patients admitted to the hospital with severe TBI during year 2000. In total, 50 patients were admitted with severe TBI. Twenty-seven out of these had complete platelet counts at admission and 24 hours thereafter and were included for further study. We found thrombocytopenia at admission to be a risk factor for PHI (p=0.008). We also found that the platelet count decreased more significantly during the first 24 h after injury in patients with PHI compared to patients without PHI (p=0.009). A trend towards longer periods of mechanical ventilation in patients with PHI compared to patients without PHI was identified. These findings support a causal relationship between thrombocytopenia and PHI. The findings provide a rationale for future studies of hemostatic agents in the treatment of TBI in order to minimise complications caused by PHI.

Blood Coagulation Tests↗

Intracerebral microdialysis in severe brain trauma: the importance of catheter location.

OBJECT: Intracerebral microdialysis has attracted increasing interest as a monitoring technique during neurological/neurosurgical intensive care. The purpose of this study was to compare cerebral energy metabolism, an indicator of secondary excitotoxic injury and cell membrane degradation close to focal traumatic lesions ("penumbra zones") and in remote and apparently intact brain regions of the ipsilateral and contralateral hemispheres. METHODS: The study included 22 consecutive patients with a mean age 44 +/- 17 years and an estimated postresuscitation Glasgow Coma Scale motor score less than 5. Altogether 40 microdialysis catheters with radiopaque tips were inserted. Two catheters could not be localized on postoperative computerized tomography (CT) scans and were excluded from the analysis. The perfusates were analyzed at the patient's bedside for levels of glucose, pyruvate, lactate, glutamate, and glycerol with the aid of a CMA 600 Analyzer. The positions of eight (22%) of the 36 catheters were reclassified after a review of findings on CT scans. Except for pyruvate the values of all biochemical variables and the lactate/pyruvate (L/P) ratio were significantly different in the penumbra zone when compared with mean values found in "normal" tissue ipsilateral to the parenchymal damage and in contralateral normal tissue (p < 0.001). In the penumbra zone a slow normalization of the L/P ratio and levels of glutamate and glycerol were observed. In normal tissue these parameters remained within normal limits. CONCLUSIONS: Data obtained from intracerebral microdialysis can be correctly interpreted only if the locations of the catheters as they relate to focal brain lesions are visualized. A "biochemical penumbra zone" surrounds focal traumatic brain lesions. It remains to be proven whether therapeutic interventions can protect the penumbra zone from permanent damage.

Adult↗

Transcranial Doppler sonography pulsatility index (PI) reflects intracranial pressure (ICP).

BACKGROUND: In patients with intracranial pathology, especially when comatose, it is desirable to have knowledge of the intracranial pressure (ICP). To investigate the relationship between ICP and transcranial Doppler (TCD) derived pulsatility index (PI) in neurosurgical patients, a prospective study was performed on patients admitted to our neurointensive care unit. METHODS: Daily TCD mean flow velocity (mFV) measurements were made. TCD measurements were routinely performed bilaterally on the middle cerebral artery (MCA). PI (peak systolic-end diastolic velocities/mean flow velocity) was calculated. RESULTS: Eighty-one patients with various intracranial disorders who had an intraventricular catheter for registration of the ICP were investigated: 46 (57%) patients had subarachnoid hemorrhage, 21 (26%) patients had closed head injury, and 14 (18%) patients had other neurosurgical disorders. A total of 658 TCD measurements were made. ICP registrations were made parallel with all TCD measurements. A significant correlation (p < 0.0001) was found between the ICP and the PI with a correlation coefficient of 0.938: ICP = 10.93 x PI - 1.28. In the ICP interval between 5 to 40 mm Hg the correlation between ICP and PI enabled an estimation of ICP from the PI values with an SD of 2.5. The correlation between the cerebral perfusion pressure (CPP) and PI was significant (p < 0.0001) with a correlation coefficient of -0.493. When separating the measurements in severely elevated (>120 cm/s) and subnormal (<50 cm/s) TCD mFV values, the correlation coefficient between ICP and PI was 0.828 (p < 0.002) and 0.942 (p < 0.638), respectively. CONCLUSIONS: Independent of the type of intracranial pathology, a strong correlation between PI and ICP was demonstrated. Therefore, PI may be of guiding value in the invasive ICP placement decision in the neurointensive care patient.

Adolescent↗

Cerebral energy metabolism during transient hyperglycemia in patients with severe brain trauma.

OBJECTIVE: To study whether transient hyperglycemia adversely affects cerebral energy metabolism in patients with severe traumatic brain lesions. DESIGN AND SETTING: Prospective, nonrandomized study in the neurosurgical intensive care unit of a university hospital. PATIENTS: 108 patients treated for severe traumatic brain lesions. INTERVENTIONS: All patients were treated according to neurosurgical intensive care routine including monitoring of intracranial pressure. One microdialysis catheter was inserted via a burr hole frontally to that used for the intraventricular catheter ("better" position). In patients with focal lesions one or more catheters were inserted into cerebral cortex surrounding an evacuated focal contusion or underlying an evacuated hematoma ("worse" position). Perfusion rate was 0.3 micro l/min and samples were taken every 30 or 60 min. The levels of glucose, pyruvate, lactate, glutamate, and glycerol were analyzed and displayed bedside. MEASUREMENTS AND RESULTS: There were 18 episodes of moderate (12-15 mmol/l) and 6 episodes of pronounced (>15 mmol/l) hyperglycemia. Moderate hyperglycemia did not change intracerebral levels of lactate, pyruvate, glutamate, glycerol, or lactate/pyruvate ratio. Lactate concentrations increased during pronounced hyperglycemia. Pronounced cerebral lactic acidosis and a moderate increase in interstitial glycerol concentration indicating cell membrane degradation was observed in a single patient with pronounced, long-lasting hyperglycemia. CONCLUSIONS: Cerebral energy metabolism was affected by transient hyperglycemia only at blood glucose concentration above 15 mmol/l as shown by a moderate increase in interstitial lactate level.

Blood Glucose↗

Assessment of the lower limit for cerebral perfusion pressure in severe head injuries by bedside monitoring of regional energy metabolism.

BACKGROUND: In patients with severe traumatic brain lesions, the lower limit for cerebral perfusion pressure (CPP) is controversial. The aim of this prospective study was to assess this limit from bedside measurements of cerebral energy metabolism and to clarify whether the penumbra zone surrounding a focal lesion is more sensitive to a decrease in CPP than less-injured areas. METHODS: Fifty patients with severe head injury were included after evacuation of an intracranial hematoma and/or focal brain contusion. They were treated according to intensive care routine (Lund concept), including continuous monitoring of intracranial pressure. One microdialysis catheter was inserted in less-injured brain tissue ("better" position), and one or two catheters were inserted into the boundary of injured cerebral cortex ("worse" position). Concentrations of glucose, pyruvate, and lactate were analyzed and displayed bedside and were related to CPP (n = 29,495). RESULTS: Mean interstitial glucose concentration was unaffected by the level of the CPP within the studied ranges. Increases in lactate concentration (P = 0.0008) and lactate-pyruvate ratio (P = 0.01) were obtained in the "worse" but not in the "better" position at CPP less than 50 mmHg compared with the same positions at CPP greater than 50 mmHg. CONCLUSIONS: The study results support the view that CPP may be reduced to 50 mmHg in patients with severe traumatic brain lesions, provided that the physiologic and pharmacologic principles of the Lund concept are recognized. In the individual patient, preservation of normal concentrations of energy metabolites within cerebral areas at risk can be guaranteed by intracerebral microdialysis and bedside biochemical analyses.

Adolescent↗