Brain tissue oxygen monitoring: a study of in vitro accuracy and stability of Neurovent-PTO and Licox sensors

Object

Periods of brain tissue ischemia are common after severe head injury, and their occurrence and duration are negatively correlated with outcome. Accurate and reliable measurement of brain tissue oxygenation (B_ti pO₂) may be a key to improve patient outcome after severe head injury. Knowledge of stability and accuracy of the B_ti pO₂ systems is crucial. We have therefore conducted a bench test study of new Neurovent-PTO® (NV) and Licox® (LX) oxygen tension catheters to evaluate the sensor accuracy, response time to different oxygen tensions, response to temperature changes and long-term stability.

Methods

For all experiments five new fluorescent NV sensors and five new electrochemical LX sensors were used. The catheter probes were placed into a container filled with a buffer solution. The solution was equilibrated with five high precision calibration gases. The accuracy of the probes was recorded after an equilibration period of 20 min in O₂ concentrations of 5, 10, 20, 30 and 40 mmHg at 37.0?±?0.2°C. The probe response to an increase in temperature from 37.0°C to 38.5°C to 40.0°C in two different gases with O₂ concentrations of 10 and 20 mmHg were analysed. We also recorded the time for reaching 90% of a new oxygen concentration level when switching from one concentration to another. Finally, to test if there was a time-dependant drift in pO₂ recordings, all sensors were left in 10 mmHg O₂ solution for 10 days, and recordings were taken every 24 h.

Results

In all gas concentrations, NV and LX sensors measured pO₂ with high accuracy and stability in vitro (mean differences from calculated values were for NV 0.76–1.6 mmHg and for LX ?0.46–0.26 mmHg). Both sensors showed a shorter response time to pO₂ increase (for NV 56?±?22 s and for LX 78?±?21 s) compared to pO₂ decrease (for NV 131?±?42 s and for LX 215?±?63 s). NV pO₂ values were more stable for changes in temperature, while LX sensors showed larger standard deviations with increasing temperature (the difference from the calculated values in 19.7 mmHg O₂ at 40°C were for NV probes between 0.5 and 1.7 mmHg and LX between ?2.3 and 1.9 mmHg). Both sensors gave stable results with low standard deviations during long-term (10 days) use, but with a slight elevation of measured pO₂ levels by time.

Conclusions

Both NV and LX were accurate in detecting different oxygen tensions, and they did not deviate over longer recording times. However, LX needed a significantly longer time to detect changes in pO₂ levels compared to NV. Furthermore, LX probes showed an increased standard deviation with higher temperatures.     

Analysis of oxygen transport and oxygen utilization combined

We propose a model which combines oxygen transport system from blood to tissue with oxygen utilization system at the tissue.The model consists of 3 equations; the relationship between tissue P_{O 2} (Pts_{O 2}) and O₂ utilization (Vrc_{O 2}), diffusion from vessel to tissue, and Fick equation. This model has two advantages. First, it is self-consistent. Varying Vrc_{O 2} varies the oxygen transport. Second, it enables to analyze the effects of various factors of oxygen transport/utilization on other factors.We applied this model to the brain tissue. Following values were assumed. Critical tissue P_{O 2} (Pcrit_{O 2}) 2mmHg; oxygen utilization above this level 3ml·min^–1·100g^–1; diffusion coefficient from blood vessel to tissue (D) 0.2ml·min^–1·mmHg^–1·100g^–1; cerebral blood flow (CBF) 50ml·min^–1·100g^–1; hemoglobin 15g·100ml^–1. Hill equation was used for oxygen dissociation curve with n of 2.7 and P50 of 27.0mmHg.From these, the following values were obtained; Pv_{O 2}, Pts_{O 2} and Vrc_{O 2}. The changes were analyzed for the 5 input values, Pa_{O 2}, CBF, D, P50 and Hb, changing from zero to their respective normal values. A reduction of a single parameter down to 50% of normal barely affected oxygen utilization. A further reduction resulted in significant oxygen utilization. Under conditions studied, a decrease in P50 reduced oxygen utilization faster than that in any other parameters.(Suwa K: Analysis of oxygen transport and oxygen utilization combined. J Anesth 6: 51–56, 1992)     

Relevance of ICP and ptiO<Subscript>2</Subscript> for indication and timing of decompressive craniectomy in patients with malignant brain edema

Summary Background. The exact effects of decompressive craniectomy on intracranial pressure (ICP) and cerebral tissue oxygenation (ptiO₂) are still unclear. Therefore, we have monitored ICP and ptiO₂ intra-operatively and correlated these values to different operative steps during craniectomy.Methods. ICP and ptiO₂ values have been monitored both, simultaneously and continuously, in 15 patients with cerebral edema due to posttraumatic or postischemic brain swelling. Indications for craniectomy were an increase in ICP above 25 mmHg or a decrease in ptiO₂ below 10 mmHg resistant to conservative treatment (e.g. mannitol, hyperventilation, adequate arterial blood oxygenation, etc.). In all cases, we performed a fronto-temporo-parietal craniectomy (15×12 cm) and dura enlargement with galea-periosteum. During craniectomy, monitoring of ICP and ptiO₂ in the affected hemisphere was continued. Values were recorded and correlated with the different operative steps.Findings. We performed craniectomy according to our treatment protocol in 5 patients. Prior to surgery, mean ICP values were 25.6 mmHg (range: 23–29 mmHg), mean ptiO₂ values were 5.9 mmHg (range: 2.4–9.5 mmHg), and mean CPP values were 66 mmHg (range: 60–70 mmHg). After removing the bone flap, ICP values dropped to physiological values (mean: 7.4 mmHg), whereas ptiO₂ values increased only slightly (mean: 11 mmHg). Opening of the dura resulted in a further decrease of ICP (mean 4.8 mmHg) and an increase of ptiO₂ to normal limits (mean: 18.8 mmHg). After skin closure, mean ICP was 6.8 mmHg and mean ptiO₂ was 21.7 mmHg, respectively. We found a significant decrease of ICP after craniectomy (p<0.042) and after dura enlargement (p<0.039) as well as a statistically significant increase in ptiO₂ after craniectomy (p<0.043) and after dura enlargement (p<0.041).Conclusion. As a large bone flap in decompressive craniectomy is essential for adequate ICP reduction, the results of the presented cases suggest that dura enlargement is the crucial step to restore adequate brain tissue oxygenation and that ptiO₂ monitoring could be an important tool for timing craniectomy in the future.     

Carbon dioxide analysers: accuracy,alarm limits and effects of interfering gases

Six mainstream and twelve sidestream infrared carbon dioxide (CO₂) analysers were tested for accuracy of the CO₂ display value, alarm activation and the effects of nitrous oxide (N₂O), oxygen (O₂) and water vapour according to the ISO Draft International Standard (DIS) #9918. Mainstream analysers (M-type): Novametrix Capnogard 1265; Hewlett Packard HP M1166A (CO₂module HP M1016A); Datascope Passport; Marquette Tramscope 12; Nellcor Ultra Cap N-6000; Heilige Vicom-sm SMU 611/612 ETC. Sidestream analysers: Brüel &; Kjaer Type 1304; Datex Capnomac II; Marquette MGA-AS; Datascope Multinex; Ohmeda 4700 OxiCap (all type S1: respiratory cycles not demanded); Biochem BCI 9000; Bruker BCI 9100; Dräger Capnodig and PM 8020; Criticare Poet II; Heilige Vicom-sm SMU 611/612 A-GAS (all type S2: respiratory cycles demanded). The investigations were performed with premixed test gases (2.5, 5, 10 vol%, error ?1% rel.). Humidification (37° C) of gases were generated by a Dräger Aquapor. Respiratory cycles were simulated by manually activated valves. All monitors complied with the tolerated accuracy bias in CO₂ reading (≤ 12% or 4 mmHg of actual test gas value) for wet and dry test gases at all concentrations, except that the Marquette MGA-AS exceeded this accuracy limit with wet gases at 5 and 10 vol% CO₂. Water condensed in the metal airway adapter of the HP M1166A at 37° C gas temperature but not at 3(P C. The Servomex 2500 (nonclinical reference monitor), Passport (M-type), Multinex (S1-type) and Poet II (S2-type) showed the least bias for dry and wet gases. Nitrous oxide and O₂ had practically no effect on the Capnodig and the errors in the others were max. 3.4 mmHg, still within the tolerated bias in the DIS (same as above). The difference between the display reading at alarm activation and the set point was in all monitors (except in the Capnodig: bias 1.75 mmHg at 5 vol% CO₂) below the tolerated limit of the DIS (difference ≤ 0.2 vol%). The authors conclude that the tested monitors are safe for clinical use (except those failing the DIS limits). The accuracy of the CO₂-reading (average of mean absolute bias) is better in the M-type than in the S1- or S2- type analysers although no statistical (nor clinical) significant differences could be detected. Most manufacturers work with stricter limits than those proposed by the DIS.     

Differential response of bone cells isolated by sequential digestion to dichloromethylenebisphonate in culture

Summary Dichloromethylenebisphosphonate (Cl₂MBP), a compound structurally related to inorganic pyrophosphate but resistant to hydrolysis of endogenous phosphatase to yield inorganic phosphate, inhibits bone resorption and soft tissue mineralizationin vivo. Previously, we have shown that bone cells isolated from rat calvaria respond profoundly to the exposure of Cl₂MBP. To determine whether the cellular effects evoked by Cl₂MBP are confined to a particular bone cell type, calvaria from 1 day postnatal rats were subjected to a sequential time-dependent enzyme digestion, yielding five bone cell populations marked by differences in PTH response, alkaline phosphatase activity and collagen, as well as hyaluronic acid synthesis. Culturing these bone cell populations with Cl₂MBP revealed that previously observed results found with mixed bone cells (inhibition of cell proliferation, diminution of hyaluronic acid synthesis, and increase in alkaline phosphatase) were limited to cell populations which, according to the isolation scheme, stem from the outer tissue layer(s) of the calvaria. Collagen synthesis, however, was found to be equally increased regardless of cell type. These present results indicate that the action of Cl₂MBP on bone may be cell specific.     

Fast method for longitudinal relaxation time and water content mapping of the human brain on a clinical MR scanner

Summary. Background. Longitudinal relaxation time (T₁) map generation from human brain slices renders possible the in vivo follow-up of the changes in T₁ values during the course of several pathologies such as stroke, multiple sclerosis, traumatic brain injury etc. T₁ values can be converted to water contents, thus brain oedema reducing therapy can be non-invasively evaluated. The purpose of the study was to work out a fast and simple MRI method to obtain T₁ and water maps of the human brain.Method. The T₁ values of Gadolinium solutions with different concentrations were determined by means of MRI methods at a clinical MR scanner operating at 1 Tesla. In order to validate these measurements, T₁ values of the same Gadolinium solutions were also quantified with a relaxometer operating at the same field strength. T₁ and water maps from the brains of healthy volunteers were obtained with an inversion prepared spoiled gradient echo sequence (turbo-FLASH).Findings. The T₁ values of Gadolinium solutions measured with the relaxometer showed a strong correlation (r>0.999) with those determined with MRI sequences on the whole body scanner. The fastest MRI method to produce T₁ and consequent water maps from human brain was the inversion prepared turbo-FLASH sequence.Conclusions. The implemented turbo-FLASH method can produce T₁ and water map of a single virtual brain slice within 2 minutes. However, brain tissue containing haemorrhage should be excluded from the measurement due to the large influence of excessive haemoglobin concentration on longitudinal relaxation. The proposed method is available on most of the MR scanners, thus T₁ and water mapping of human brain can be routinely performed.     

The loss and progressive recovery of voiding after spinal cord interruption in rats is associated with simultaneous changes in autonomous contractile bladder activity

Background

Autonomous contractile activity (ACA) is a well-known phenomenon in isolated bladders from different species and seems to be important in the physiology of both normal and dysfunctional voiding.

Objective

To determine whether ACA is changed in bladders from paraplegic rats at different periods post–spinal cord injury (post-SCI).

Design, setting, and participants

ACA was studied in bladders (at least six per group) from normal and paraplegic female Wister rats at different times post-SCI (2 h, 24 h, 1 wk, and 3 wk). A group of normal rats was used as a control group. For measurements bladders were incubated in organ baths under standardised conditions.

Measurements

ACA was measured as pressure change, which was defined as either a transient change or a spiked change according to its characteristics. The effects of intravesical volume load and muscarinic agonists were studied.

Results and limitations

Following spinal cord injury (SCI) a clear evolution in ACA was observed. In bladders from SCI rats in the acute areflexive voiding phase (1 wk post-SCI), we observed decreased ACA associated with a highly increased compliance and a changed response to muscarinic agonists. ACA in bladders from SCI rats with renewed voiding reflexes (3 wk post-SCI) was increased, together with a moderately increased compliance and a (moderately) changed response to muscarinic agonists.

Conclusions

From these observations it is apparent that SCI leads to alterations in the behaviour and muscarinic response of ACA in the isolated bladder. These changes in ACA may play an important role in the pathophysiology of overactive bladder disease (OAB), and interacting with changed ACA might be promising in the search for newer treatments for OAB.     

Vitamin D deficiency in the chick embryo: Effects on prehatching motility and on the growth and differentiation of bones,muscles, and parathyroid glands

Summary Vitamin D-deficient chicken embryos were obtained by feeding laying hens diets in which 3–7 μg calcitriol replaced the vitamin D₃ supplement. A large proportion of the D-deficient embryos failed to complete the prehatching positional changes required to start pulmonary respiration. For this reason most of them became cyanotic and had subcutaneous edema and hemorrhages in the head and neck and died without hatching. Total as well as leg-bone and muscle weights were significantly lower in the deficient embryos than in the controls and these changes probably explain the inability of the embryos to complete the movements required to place the beak in contact with the air chamber and start pulmonary respiration. The histological study of the tibiae showed decreased mineralization with narrower trabeculae and enlarged osteoid seams; bone resorption at the inner surface was also significantly decreased. The ultrastructural study of parathyroid glands showed increased functional activity reflected by increased number and size of cisternae of rough endoplasmic reticulum. Injection of 10 ng calcitriol, 1 μg 24, 25-(OH)₂D₃, or 2 μg 25OHD₃ to deficient embryos on the 14th day of incubation improved hatchability, bone and muscle weights, and both bone mineralization and resorption.     

Brain protection: physiological and pharmacological considerations. Part I: The physiology of brain injury

Ischaemia, whether focal or global in nature, produces a sequence of intracellular events leading to increased cell permeability to water and ions including Ca++. There is a loss of cellular integrity and function, with increased production of prostaglandins, free radicals, and acidosis with lactate accumulation. These events may be exacerbated by glucose administration. Pharmacological agents aimed at alleviating ischaemic injury could be directed at decreasing cerebral metabolic requirements for oxygen, improving flow to ischaemic areas, preventing Ca+(+)-induced injury, inhibition of free radical formation, lactate removal, inhibition of prostaglandin synthesis, and prevention of complement-mediated leukocyte aggregation. Part I of this paper describes some of the pathophysiological events leading to ischaemic brain injury. Part 2 of this paper will consider the current agents available for brain protection.     

Increased tissue oxygen extraction and acidosis with progressive severity of sepsis

BACKGROUND: Lactic acidosis and increased production of CO(2) are common in septic shock. Presumably, both acidosis and CO(2) enhance the release of oxygen from hemoglobin. The purpose of this study was to assess the relationship of oxygen utilization, CO(2) production, acidosis, and hemoglobin oxygen (Hgb-O(2)) dissociation with progressive severity of sepsis to shock. MATERIALS AND METHODS: Femoral arterial and vein, hepatic vein, portal vein, and pulmonary artery catheters were placed in 16 anesthetized swine. Organ blood flow was determined by timed injections of colored microspheres. After baseline measurements, Pseudomonas aeruginosa was infused in eight animals. This bacterial slurry was continued inciting a progression of sepsis to shock. Eight animals served as instrumented controls. RESULTS: With sepsis and shock, there was a progressive decrease in pH and an increase in pCO(2) in plasma with all sampling sites (P < 0.01 septic shock versus baseline versus control). Blood flow to the liver and intestines increased with sepsis (P < 0.01) but then returned to near baseline control values during shock. VO(2) and/or percent O(2) extraction increased with sepsis and septic shock for the whole body and for the liver, intestine and leg (P < 0.01). There was a strong correlation between venous O(2) saturation, acidosis, and pCO(2) to percent O(2) extraction (r > 60; P < 0.0001). However, calculated P(50) values for Hgb-O(2) dissociation remained unchanged. CONCLUSIONS: This study demonstrates that increased oxygen extraction in severe sepsis is related to a fall in tissue oxygen availability and not related to any allosteric change in Hgb-O(2) dissociation. Therefore, acidosis and hypercapnia do not have a demonstrable effect on altering oxygen availability during sepsis.     

Comparison of the effects of 1,25-dihydroxycholecalciferol,prostaglandin E2, and osteoclast-activating factor with parathyroid hormone on the ultrastructure of osteoclasts in cultured long bones of fetal rats

Summary The effects of 1,25-dihydroxy vitamin D₃ [1,25(OH)₂D₃], prostaglandin (PGE₂), and osteoclast-activating factor (OAF) on the size of osteoclasts, nuclei, ruffled borders, and clear zones in cultured long bones of fetal rats were quantitated. In addition, the number of osteoclasts in the bones was counted and the release of calcium from the bone into the culture medium was determined. These data were compared with the corresponding effects of parathyroid hormone (PTH). All agents tested increased the size of the ruffled borders significantly after 3 h, the size of the clear zones after 12 h, and the size of the cells after 12–24 h. No important differences in sizes were noticed between the agents tested or between the agents and PTH. The number of osteoclasts was increased after 24 h of treatment with PTH, but not after the other agents. Calcium release was significantly increased for all agents between 12 and 24 h. It is concluded that bone resorption by 1,25(OH)₂D₃, OAF, and PGE₂ is mediated primarily by increased activity of existing osteoclasts similar to PTH activation.     

Cerebral blood flow in Moyamoya disease part 2: Autoregulation and CO2 response

Summary In order to clarify the cerebrovascular response in Moyamoya disease, the autoregulation and CO₂ response was investigated using the^81mKr continuous cerebral blood flow (CBF) measurement technique.A total of 32 measurements were made over the anterior and posterior circulation in 16 Moyamoya patients (seven adults, nine children). CBF measurements were made during four loading trials (hypertension, hypotension, CO₂ inhalation and hyperventilation). Study was then made of the vascular response of the frontal lobe, perfused by the internal carotid artery (ICA), and the occipital lobe and cerebellum, perfused by the vertebral artery (VA).Deficits of autoregulation were more severe among the juvenile cases in response to hypotension than to hypertension in both the ICA and VA regions, but the deficits were mild. The CO₂ response to hypercapnea in the juvenile cases tended to be abnormal in both the ICA and VA regions. Both adult and juvenile patients showed deficits in the ICA region in response to hyperventilation, some of whom exhibited paradoxial responses.Notable differences in the severity of the deficits of the vascular response in adult and juvenile cases were seen, with the deficits in the response being more severe among the juvenile cases. Moreover, significant regional differences in the deficits were also found.     

Microvascular in vivo assessment of reperfusion injury: significance of prostaglandin E(1) and I(2) in postischemic "no-reflow" and "reflow-paradox"

BACKGROUND: Microvascular ischemia-reperfusion (I/R) injury is characterized by failure of capillary perfusion ("no-reflow") and reoxygenation-associated phenomena ("reflow-paradox"), including activation of leukocyte-endothelium interaction with cytotoxic mediator-induced loss of endothelial integrity. The objectives of this study were to elucidate the impact of both prostaglandins E(1) (PGE(1)) and I(2) (PGI(2)) in microvascular reperfusion injury, with special focus on the distinct pathophysiology of no-reflow- and reflow-paradox phenomena. MATERIALS AND METHODS: By use of the hamster dorsal skinfold preparation and in vivo fluorescence microscopy, the microcirculation of a striated skin muscle was assessed before 4 h of pressure-induced ischemia and 0.5, 2, and 24 h after onset of reperfusion. RESULTS: I/R was characterized by enhanced leukocyte-endothelium interaction in postcapillary venules, increase of macromolecular leakage, and reduction of functional capillary perfusion (P < 0.05). Intravenous 2-h infusion of PGE(1), starting with onset of reperfusion, reduced leukocyte adhesion and macromolecular leakage in postcapillary venules during early reperfusion (P < 0.05), while 6-h infusion, given during ischemia and early reperfusion, showed no significant effects. PGI(2) infusion also attenuated postischemic leukocyte adhesion, which was significant by a 6-h prolonged administration (P < 0.05), but did not influence the increase of microvascular permeability. Both prostaglandins were unable to prevent the postischemic failure of capillary perfusion (no-reflow). CONCLUSIONS: Both prostaglandins did not significantly influence postischemic no-reflow phenomena, but appeared as potent inhibitors of reflow-paradox under the experimental circumstances of this study.