A. Rieger

Efficiency of 7.2% hypertonic saline hydroxyethyl starch 200/0.5 versus mannitol 15% in the treatment of increased intracranial pressure in neurosurgical patients – a randomized clinical trial [ISRCTN62699180]

IntroductionThis prospective randomized clinical study investigated the efficacy and safety of 7.2% hypertonic saline hydroxyethyl starch 200/0.5 (7.2% NaCl/HES 200/0.5) in comparison with 15% mannitol in the treatment of increased intracranial pressure (ICP).MethodsForty neurosurgical patients at risk of increased ICP were randomized to receive either 7.2% NaCl/HES 200/0.5 or 15% mannitol at a defined infusion rate, which was stopped when ICP was < 15 mmHg.ResultsOf the 40 patients, 17 patients received 7.2% NaCl/HES 200/0.5 and 15 received mannitol 15%. In eight patients, ICP did not exceed 20 mmHg so treatment was not necessary. Both drugs decreased ICP below 15 mmHg (p < 0.0001); 7.2% NaCl/HES 200/0.5 within 6.0 (1.2–15.0) min (all results are presented as median (minimum-maximum range)) and mannitol within 8.7 (4.2–19.9) min (p < 0.0002). 7.2% NaCl/HES 200/0.5 caused a greater decrease in ICP than mannitol (57% vs 48%; p < 0.01). The cerebral perfusion pressure was increased from 60 (39–78) mmHg to 72 (54–85) mmHg by infusion with 7.2% NaCl/HES 200/0.5 (p < 0.0001) and from 61 (47–71) mmHg to 70 (50–79) mmHg with mannitol (p < 0.0001). The mean arterial pressure was increased by 3.7% during the infusion of 7.2% NaCl/HES 200/0.5 but was not altered by mannitol. There were no clinically relevant effects on electrolyte concentrations and osmolarity in the blood. The mean effective dose to achieve an ICP below 15 mmHg was 1.4 (0.3–3.1) ml/kg for 7.2% NaCl/HES 200/0.5 and 1.8 (0.45–6.5) ml/kg for mannitol (p < 0.05).Conclusion7.2% NaCl/HES 200/0.5 is more effective than mannitol 15% in the treatment of increased ICP. A dose of 1.4 ml/kg of 7.2% NaCl/HES 200/0.5 can be recommended as effective and safe. The advantage of 7.2% NaCl/HES 200/0.5 might be explained by local osmotic effects, because there were no clinically relevant differences in hemodynamic clinical chemistry parameters.

Influence of moderate and profound hyperventilation on cerebral blood flow, oxygenation and metabolism

OBJECTIVE The aim of the present study was to examine the impact of moderate and profound hyperventilation on regional cerebral blood flow (rCBF), oxygenation and metabolism. MATERIALS AND METHODS Twelve anesthetized pigs were subjected to moderate (mHV) and profound (pHV) hyperventilation (target arterial pO(2): 30 and 20 mmHg, respectively) for 30 min each, after baseline normoventilation (BL) for 1 h. Local cerebral extracellular fluid (ECF) concentrations of glucose, lactate, pyruvate and glutamate as well as brain tissue oxygenation (p(ti)O(2)) were monitored using microdialysis and a Licox oxygen sensor, respectively. In nine pigs, regional cerebral blood flow (rCBF) was also continuously measured via a thermal diffusion system. RESULTS Both moderate and profound hyperventilation resulted in a significant decrease in rCBF (BL: 37.9+/-4.3 ml/100 g/min; mHV: 29.4+/-3.6 ml/100 g/min; pHV: 23.6+/-4.7 ml/100 g/min; p<0.05) and p(ti)O(2) (BL: 22.7+/-4.1 mmHg; mHV: 18.9+/-4.9 mmHg; pHV: 13.0+/-2.2 mmHg; p<0.05). A p(ti)O(2) decrease below the critical threshold of 10 mmHg was induced in three animals by moderate hyperventilation and in five animals by profound hyperventilation. Furthermore, significant increases in lactate (BL: 1.06+/-0.18 mmol/l; mHV: 1.36+/-0.20 mmol/l; pHV: 1.67+/-0.17 mmol/l; p<0.005), pyruvate (BL: 46.4+/-7.8 micromol/l; mHV: 58.0+/-10.3 micromol/l; pHV: 66.1+/-12.7 micromol/l; p<0.05), and lactate/glucose ratio were observed during hyperventilation. (Data are presented as mean+/-S.E.M.) CONCLUSIONS Both moderate and profound hyperventilation may result in insufficient regional oxygen supply and anaerobic metabolism, even in the uninjured brain. Therefore, the use of hyperventilation cannot be considered as a safe procedure and should either be avoided or used with extreme caution.

Brain tissue oxygen monitoring for assessment of autoregulation: Preliminary results suggest a new hypothesis

Brain tissue oxygen monitoring (PtiO2 (Neurotrend, Codman, Germany) was employed in addition to standard intracranial pressure (ICP) and cerebral perfusion pressure (CPP) monitoring in seven patients with severe neuronal damage of heterogeneous etiology. The correlation between PtiO2 changes and CPP fluctuations during periods of 30 minutes were analyzed, when CPP was above 70 mmHg and lower than 100 mmHg. A new ratio, the CPP-oxygen-reactivity (COR) index was calculated as COR=&Dgr;ptiO2%/&Dgr;CPP%. The patient COR values were compared to those found in the brain of six noninjured anesthetized piglets. The analysis was performed to determine the significance of synchronous fluctuations of CPP and PtiO2, when CPP is above the lower threshold of autoregulation. The correlation between CPP variations and ptiO2 variations was found to be strong (Rmean = 0.74 ± 0.17) in the patients and was weak in the uninjured animals (Rmean=0.38 ± 0.43). The CORmean was 2.05 ± 0.57 in patients and 0.78 ± 0.6 in the animals. In the injured brain of our patients, we observed an unexpectedly close correlation between PtiO2 and CPP variations when CPP levels were within a therapeutically targeted range (70 to 100 mmHg). In a porcine model, we could not find this relationship in the noninjured brain. We speculate that an increased COR might be indicative for an impaired local pressure autoregulation. The preliminary data suggest that COR values above “1” might be pathologic. However, the reported sample sizes are too small to provide sufficient statistical power to justify inferential statistical analyses. As such, results are presented with descriptive statistics only, and should be regarded as a hypothesis.

Factors predicting pituitary adenoma invasiveness in acromegalic patients

Forty-four adult acromegalic patients carrying growth hormone-producing pituitary macroadenomas were investigated with neuroradiological and endocrinological techniques. Plasma growth hormone and somatomedin-C levels were repeatedly measured before surgical removal of tumors and during the follow-up period. Twenty-five patients presented preoperatively with an invasive adenoma that involved the cavernous sinus (CS). Diagnosis of tumor invasivity was made according to distinct neuroradiological criteria and was confirmed or rejected during surgery. Significantly higher basal growth hormone levels were found in patients with CS invasion than in cases without tumor growth in the CS. Evidence is presented that plasma growth hormone level in acromegalics is a more sensitive indicator for predicting tumor invasiveness than somatomedin-C. Growth hormone basal values before surgery and the extent of their decrease after removal of tumor correlate with adenoma growth in the parasellar compartments and should be used as a prognostic factor to aid in planing adjuvant tumor treatment.

Experiences with continuous intra-arterial blood gas monitoring: precision and drift of a pure optode-system

OBJECTIVE The utility of continuous intra-arterial blood gas analysis (CBGA) with combined electrochemical and optode sensors has been demonstrated. More recently, a pure optode sensor with a changed sensing element architecture has become available. The aim was to determine the measurement accuracy and long-term stability of the new sensor. DESIGN A prospective explorative study was performed. Simultaneous measurements of intermittent blood gas analyses (IBGA) (ABL 610, Radiometer, Copenhagen) and CBGA (Diametrics Medical, High Wycombe, Bucks., UK) were compared using Bland-Altman analysis. PATIENTS Twenty-five patients admitted to the ICU and requiring mechanical ventilation for an expected minimum of about 96 h were included. RESULTS Mean monitoring time was 106.1 (range 15-231) hours. Bias and precision for PO(2 )were -0.2 kPa (1%)+/-1.8 kPa (9.5%); PCO(2): 0.03 kPa (0.6%)+/-0.44 kPa (9.3%); pH: -0.001 (0.01%)+/-0.04 (0.45%). The sensor showed no change of measurement characteristics during 4 days of measurement. However, in 69 cases continuous monitoring was interrupted (reversible sudden drops of PO(2) measurement) possibly caused by thrombotic deposition and/or sensor bending and accidental sensor retraction. CONCLUSIONS The precision and bias of the PCO(2)- and pH-sensing elements were in line with the findings of the older sensor technology. The possibility that the PO(2) optode could offer greater accuracy than the older technology is suggested by comparisons with results reported in previous studies. No sensor drift occurred during long-term measurement over more than 4 days.

Simultaneous Continuous Measurement of pO2, pCO2, pH and Temperature in Brain Tissue and Sagittal Sinus in a Porcine Model

INTRODUCTION The clinical use of brain tissue oxygen measurement in patients with severe head injury is increasing. It is important to compare the findings in brain tissue with cerebrovenous blood oximetry, to obtain normal values and to find out limitations of the method. We evaluated a newly available multisensor probe simultaneously in the brain tissue and in the sagittal sinus in a porcine animal model. METHODS We placed the Paratrend 7-probe (BSL, High Wycombe, UK) in the left frontoparietal white matter and measured pO2 (PtiO2), pCO2 (ptiCO2), pH and temperature while simultaneously measuring these parameters (pcvO2, pcvCO2) in the sagittal sinus in 7 pigs under general anaesthesia during oxygen enhancement. RESULTS The relation between oxygen increase in brain tissue and in the sagittal sinus showed a coefficient of correlation (CCmean) rmean = 0.96. The quantitative response in brain tissue was much more sensitive than in the sinus. A close correlation between pCO2 in brain tissue and sagittal sinus and the increase of the inspired oxygen was seen: CC ptiCO2 to arterial oxygen pressure (paO2) - rmean = 0.67, CC pcvCO2 to paO2 - rmean = 0.88. CONCLUSIONS Measuring partial oxygen pressure in brain tissue is more responsive to physiological variations, and the absolute values are more sensitive than oxygen measurement in the cerebrovenous compartment. This is important for interpreting measured values and introducing new coefficients for patient monitoring.

Cerebrovenous blood temperature-influence of cerebral perfusion pressure changes and hyperventilation: evaluation in a porcine study and in man.

The objective of the first part of this study was to use an animal model to investigate the relationship between temperature in the cerebrovenous compartment and cerebral perfusion pressure. In the second part of the study, the objective was to examine the influence of hyperventilation and hypothermia on jugular bulb temperature and body temperature in patients undergoing elective neurosurgery. Intracranial pressure was increased artificially by inflating an infratentorial supracerebellar placed balloon catheter in nine pigs under general anesthesia. Temperature was monitored by thermocouples inserted in the sagittal sinus, white matter of the left lobe and abdominal aorta during the ensuing decrease in cerebral profusion pressure (CPP). Cerebrovenous blood temperature (jugular bulb) and body temperature (urinary bladder) were simultaneously monitored in 24 patients undergoing craniotomy. Moderate hyperventilation was performed in all patients. Cerebrovenous blood and core body temperature were recorded and differences between these two temperatures calculated at the beginning and the end of hyperventilation. At the beginning of the intracranial pressure (ICP), increase mean temperatures of cerebrovenous blood and cerebral tissue (left lobe) were lower than core body temperature. During CPP reduction the difference between core body temperature and cerebrovenous blood temperature increased significantly from 0.86+/-0.44 degrees C prior to ICP rise to 1.19+/-0.58 degrees C at maximum ICP. Before hyperventilation, cerebrovenous blood temperature was higher in 19 patients (+/- difference: 0.34 degrees C +/- 0.27) and equal or lower in five patients (difference: -0.08 degrees C +/- 0.11), than core body temperature. At the end of hyperventilation, the difference between cerebrovenous blood temperature and core body temperature increased (+0.42 degrees C +/- 0.24) in those 19 patients who had started with a higher cerebrovenous blood temperature and decreased (-0.10 degrees C +/- 0. 18) in the other five patients. Both studies demonstrated that the temperature of cerebrovenous blood is influenced by maneuvers which are supposed to decrease cerebral blood flow.

Is it useful to measure supratentorial ICP in the presence of a posterior fossa lesion? Absence of transtentorial pressure gradients in an animal model

Previous studies with animal models of supratentorial ICP elevation have demonstrated a pressure gradient between the supratentorial and the infratentorial compartments. The present study was designed to investigate the possible presence of such a gradient in the case of infratentorial ICP elevation. An inflatable infratentorial balloon catheter was implanted in seven domestic pigs. The infratentorial ICP (ICPi) was measured in the left cerebellar hemisphere, and the supratentorial ICP (ICPs) was measured in the left cerebral hemisphere. The corresponding pulse amplitudes (ICPi-PA, ICPs-PA) were recorded in both compartments, and the cerebral perfusion pressure (CPP) was calculated. ICPi and ICPs values prior to balloon inflation were 4.4 (SD 2.2) and 4.1 (SD 2.3) mm Hg, respectively, and increased to 63.1 (SD 32.6) and 62.3 (SD 28.1) mmHg after balloon inflation. ICPi-PA rose from 3.1 (SD 0.43) to 12.8 (SD 8.0) mmHg, and ICPs-PA rose from 3.2 (SD 0.63) to 13.0 (SD 7.1) mmHg. CPP decreased from 86.1 (SD 12.0) to 55.4 (SD 14.6) mm Hg. The paired difference between ICPi and ICPs values was 0.44 (SD 1.96) mmHg, and the paired difference of ICP amplitudes was 0.03 (SD 1.19) mmHg. All these differences in infratentorial and supratentorial values were statistically not significant. In conclusion, infratentorial ICP elevation in the presented pig model leads to a uniform ICP elevation in the intracranial space without development of a considerable pressure gradient below and above the tentorium. In the low pressure part of the ICP curve, cerebrospinal fluid connects the compartments and contributes to the pressure equilibrium. The early obstruction of the foramen magnum by intruding cerebellar tissue seems to isolate the infratentorial from the spinal compartment. In the high-pressure part of the curve, the upwards cerebellar transtentorial herniation takes over the pressure transfer, and the whole intracranial space can be considered as a single compartment in the pig.

Continuous monitoring of the partial pressure of oxygen in cerebral venous blood

OBJECTIVE Clinical oxygen monitoring in the injured brain is somewhat difficult. However, ischemia is one of the major factors responsible for secondary tissue damage after head injury or subarachnoid hemorrhage. Therefore, the aim of the present study was to investigate the value of continuously monitoring the partial pressure of oxygen in cerebral venous blood (PcvO2) during changes in intracranial pressure (ICP). METHODS In eight domestic pigs with Clark type probes placed in the posterior third of the superior sagittal sinus, PcvO2 was continuously registered while ICP was stepwise elevated by an inflatable balloon placed below the tentorium. Arterial blood pressure was continuously monitored, cerebral perfusion pressure (CPP) was calculated, and arterial partial carbon dioxide pressure and partial pressure of oxygen were registered intermittently. RESULTS The mean intraparenchymal ICP before the start of balloon inflation was 5 +/- 1 mm Hg, the mean CPP was 80 +/- 15 mm Hg, and the mean PcvO2 was 36 +/- 3 mm Hg. At maximum ICP elevation, CPP decreased to 20 +/- 12 mm Hg, PcvO2 decreased to 10 +/- 6 mm Hg, and ICP increased to 90 +/- 10 mm Hg. Strong linear correlations between ICP and PcvO2 and between CPP and PcvO2 were revealed, and mean correlation coefficients of 0.89 for ICP/PcvO2 and 0.73 for CPP/PcvO2 were calculated. CONCLUSION The present study demonstrates that polarographic PcvO2 monitoring in the superior sagittal sinus is a reliable method for the early detection of reduced CPP during ICP elevation. This technique is capable of registering the global oxygen supply and oxygen consumption of the brain. It seems superior to jugular venous oxymetry and is better suited for clinical use because of a somewhat low artifact susceptibility.

Temperature gradient between brain tissue and arterial blood mirrors the flow-metabolism relationship in uninjured brain: an experimental study.

Background:  The purpose of the present experimental study was to determine the feasibility and usefulness of brain temperature measurement (Tbr) and the calculated difference between brain temperature and arterial blood temperature (ΔTbr‐a) in uninjured brain during variations of cerebral perfusion pressure (CPP) and concomitant changes of the regional cerebral blood flow (rCBF).