Regional cerebral blood flow after a localized cerebral contusion in pigs

Summary Regional cerebral blood flow (rCBF) in anaesthetized pigs is investigated before and after an induced focal cerebral contusion. Mean intracranial pressure increased for a short period following the contusion and reduced perfusion pressure to 60% of control pressure. Forty five minutes later the mean intracranial pressure was still high and different from the control values. Global flow and cerebral production of CO² increased concomitantly. In the cortical region where the contusion was visible macroscopically the rCBF diminished from 36.5 to 29.1 ml/min/100g. In the rest of the grey matter the rCBF raised after the contusion with an increase away from the centre of the lesion. CBF of cortical grey matter in the region symmetrically to the contusion increased significantly more than in the traumatized hemisphere. White matter rCBF changed least in the region underlying the contusion, while an increase was observed away from the contusion and on the opposite side of the brain. The correlation between tension of CO₂ in arterial blood and regional cerebral blood flow disappeared in the region of the contusion. The correlation between global metabolism and regional cerebral blood flow disappeared after the contusion in all regions. Local flow modulating factors influencing flow in the region of macroscopically visible injury has influence abating with distance from the centre of the injury together with a possible neuronally transmitted drive on flow in the opposite hemisphere.     

The effect of ketanserin on cerebral blood flow and cerebrovascular CO2 reactivity in healthy volunteers

Summary The effect of the anti-hypertensive agent ketanserin on the cerebral blood flow (CBF) and the cerebrovascular CO₂ reactivity was examined in 10 healthy volunteers. Ketanserin was administered as an intravenous bolus of 10 mg followed by an infusion of 6mg/h. Before administration CBF was measured by single photon emission computerized tomography (SPECT) of inhaled¹³³ Xenon. Then arterial CO₂ tension was subsequently decreased by voluntary hyperventilation and increased by breathing an air/CO₂ mixture. The relative changes in CBF induced by the changes in arterial CO₂ tension were estimated by the cerebral arterio-venous oxygen content difference method. One hour following the start of ketanserin infusion the SPECT measurement and CO₂ manipulations were repeated.The CO₂ reactivity (expressed as the slope of the regression line of the linear relation between CBF and PaCO₂), was unchanged, i.e. 3.2%/0.1 kPa before ketanserin and 4. 1%/0.1 kPa during ketanserin, respectively. Using regression lines from a semi-logarithmic plot the CO₂ reactivity was also unchanged 3.4%/0.1 kPa and 3.5%/0.1 kPa, respectively. Ketanserin did not change CBF. The cerebral oxygen metabolism (CMRO₂) was decreased 19% one hour after the start of infusion of ketanserin.In conclusion administration of ketanserin in a clinically relevant dose to healthy volunteers does not change the regional CBF not the cerebrovascular CO₂ reactivity, but a decrease in CMRO₂ was observed. However further studies are needed to clarify whether ketanserin in fact has a depressing effect on CMRO₂ or whether the different results are caused by methodological errors or stocastic variation.     

Regional cerebral blood flow in the pig after a localized cerebral contusion treated with barbiturates

Summary Regional cerebral blood flow determined with microsphere technique in anaesthetized pigs was measured before and after a localized cerebral contusion as well as after treatment with pentobarbital.No overall reduction in intracranial pressure or perfusion pressure was observed. Flow reduction due to pentobarbital was different in different regions with a high percentage change in the highly perfused basal structures and cortical grey matter except in the centre of the contusion where the reduction was half compared to the rest of cortical grey matter. Changes in white matter were less than in cortical grey matter but more pronounced than in the very high flow areas (choroid plexus and pineal gland). The accumulated change was greatest in the damaged region. Contralateral to the contusion, where a significant increase in flow was noticed after the contusion, there was a very low accumulated change in flow. In white subcortical matter underlying the contusion a similar low flow change was observed but this was not accompanied by as large an accumulated change as in grey cortical matter. At each fraction of injected pentobarbital a short-lasting increase in intracranial pressure and a reduction in mean arterial blood pressure was observed. The amplitude and the height of the intracranial pressure change was reduced during the pentobarbital injections.     

Effect of intraabdominal pressure elevation and positioning on hemodynamic reponses during carbon dioxide pneumoperitoneum for laparoscopic donor nephrectomy: a prospective controlled clinical study

Background Carbon dioxide (CO₂) pneumoperitoneum (PP) increases mean arterial blood pressure (MAP) and systemic vascular resistance (SVR) but decreases stroke volume (SV) and cardiac output (CO). This study evaluated the hemodynamic effects of elevated intraabdominal pressure (IAP) occurring during laparoscopic donor nephrectomy (LDN).Methods Twenty-two patients undergoing LDN were investigated and hemodynamic parameters, P_vCO₂ (carbon dioxide partial pressure), and VCO₂ (carbon dioxide production) were monitored during the procedure. Before and after PP, IAP was raised from 12 to 20 mmHg and the hemodynamic effects were measured every 30 s.Results During IAP of 12 mmHg and stable serum CO₂, there was no change in SV compared to preinsufflation levels. When IAP was elevated from 12 to 20 mmHg, SV initially decreased (p < 05), followed by an increase in MAP and SVR (p < 0.05).Conclusion This study shows that with the fluid and ventilation protocol used, PP has no significant effect on SV at an IAP of 12 mmHg, whereas increasing IAP to 20 mmHg does. In this study, the hemodynamic effects induced by CO₂ PP of 12 mmHg are not due to changes in serum CO₂ . Compression of the venous system during a PP of 20 mmHg reduces preload, with an subsequent increase in SVR.     

Brain tissue pO2 in relation to cerebral perfusion pressure,TCD findings and TCD-CO2-reactivity after severe head injury

Summary As a reliable continuous monitoring of cerebral blood flow and/or cerebral oxygen metabolism is necessary to prevent secondary ischaemic events after severe head injury (SHI) the authors introduced brain tissue pO₂ (ptiO₂) monitoring and compared this new parameter with TCD-findings, cerebral perfusion pressure (CPP) and CO₂-reactivity over time on 17 patients with a SHI. PtiO₂ reflects the balance between the oxygen offered by the cerebral blood flow and the oxygen consumption by the brain tissue. According to TCD-CO₂reactivity PtiO₂-CO₂-reactivity was introduced.After initally (day 0) low mean values (ptiO₂ 7.7 +/–2.6 mmHg, TCD 60.5 +/–32.0 cm/sec and CPP 64.5 +/–16.0 mmHg/, ptiO₂ increased together with an increase in blood flow velocity of the middle cerebral artery and CPP. The relative hyperaemic phase on days 3 and 4 was followed by a decrease of all three parameters. Although TCD-CO₂-reactivity was except for day 0 (1.4+/–1.5%), sufficient. ptiO₂-CO₂-reactivity sometimes showed so-called paradox reactions from day 0 till day 3, meaning an increase of ptiO₂ on hyperventilation. Thereafter ptiO₂-CO₂-reactivity increased, increasing the risk of inducing ischaemia by hyperventilation.The authors concluded that ptiO₂-monitoring might become an important tool in our treatment regime for patients requiring haemodynamic monitoring.     

Hemodynamic and tissue blood flow responses to long-term pneumoperitoneum and hypercapnia in the pig

Background Increased peritoneal blood flow may influence the ability of cancer cells to adhere to and survive on the peritoneal surface during and after laparoscopic cancer surgery. Carbon dioxide (CO₂) pneumoperitoneum is associated with a marked blood flow increase in the peritoneum. However, it is not clear whether the vasodilatory effect in the peritoneum is related to a local or systemic effect of CO_2. Methods In this study, 21 pigs were exposed to pneumoperitoneum produced with either CO₂ (n = 7) or helium (He) (n = 7) insufflation at 10 mmHg for 4 h, or to two consecutive levels of hypercapnia (7 and 11 kPa) (n = 7) produced by the addition of CO₂ to the inhalational gas mixture. Tissue blood flow measurements were performed using the colored microsphere technique. Results Blood flow in peritoneal tissue increased during CO₂, but not He, pneumoperitoneum, whereas it did not change at any level of hypercapnia alone. There was no change in blood flow in most organs at the partial pressure of CO₂ (PaCO₂) level of 7 kPa. However, at a PaCO₂ of 11 kPa, blood flow was increased in the central nervous system, myocardium, and some gastrointestinal organs. The blood flow decreased markedly in all striated muscular tissues during both levels of hypercapnia. Conclusion The effect of CO₂ on peritoneal blood flow during laparoscopic surgery is a local effect, and not attributable to central hemodynamic effects of CO₂ pneumoperitoneum or high systemic levels of CO₂.     

The acute effect of nimodipine on cerebral blood flow,its CO2 reactivity,and cerebral oxygen metabolism in human volunteers

Summary The present study was undertaken in 8 healthy volunteers to examine the effect of a clinically relevant dose of nimodipine (NIM) (15 and 30 microgram/kg/h) on CBF, its CO₂ reactivity, and CMRO₂. Mean arterial blood pressure (MABP) was measured intra-arterially. Regional CBF was measured by SPECT of inhaled Xenon-133. During the CO₂ reactivity tests changes in CBF were estimated by the arterio-venous-oxygen-difference method. Median CBF was 52 ml/ 100 g/min (48–53) with a normal regional distribution, and median baseline MABP was 96 mmHg (92–99). MABP was slightly reduced, by 8 mmHg (7–9), and 9 mmHg (4–11) after infusion of NIM for 2 and 4 hours, respectively. CBF, however, remained constant, although correction for changes in PaCO₂, revealed a slight increase after 4 hours (p=0.08). CMRO2 was 3.5 ml/100 g/min (3.2–3.5) and was not changed by the infusion of NIM. At arterial CO₂ tensions ranging from 4.0 to 6.5 Kpa the CO₂ reactivity was 3.0% CBF/ 0.1 kPa (2.6–3.7) and decreased significantly to 2.6% CBF/0.1 kPa (1.8–3.2) after the infusion of NIM for 3 hours (p=0.02). The median slope of the LnCBFsat/PaCO₂ relationship was 1.5 at baseline compared to 1.3 after NIM (p<0.01). No side effects were observed.The present study shows a decreased CO₂ of the cerebral vessels and a maintained coupling of CBF and CMRO₂ during the infusion of nimodipine.     

Local variations in the cerebral microcirculatory response to hypercapnia and haemorrhage

Summary This study evaluates local variations of the cerebral vasomotor responses to hypercapnia and haemorrhagic hypotension in a pig model. Four laser Doppler flow probes were used in each pig. There was considerable variation in laser Doppler signals between the four probes in baseline recordings. The increases in flow after CO₂ administration in 7 pigs had a mean coefficient of variation of 0.43 ± 0.31, and the flow changes after blood loss in another 7 pigs had a mean coefficient of variation of 0.45 ± 0.34. The range of flow changes within each animal was large; the probe with the highest CO₂ response showed on the average a 273% ± 157% larger CO₂ response than the probe with the lowest CO₂ response. Correspondingly, the probe with the best preserved blood flow after blood loss had on the average a flow value of 93% ± 12% of the baseline value, while the probe that changed most with haemorrhage had a flow value of 44% ± 24% of the baseline value. Single laser Doppler recordings have been used for the monitoring of cerebral blood flow in neurosurgical critical care, but our results suggest that a single laser Doppler flow probe is not an adequate method to monitor vasoreactivity in neurosurgical patients because flow signals from one probe may be unrepresentative for other sites in the brain.     

Cerebrovascular CO2 reactivity in elderly and younger adult patients during sevoflurane anaesthesia

Purpose

General anaesthetic agents and aging affect cerebrovascular CO₂ reactivity (CCO₂R). The purpose of this study was to investigate the effect of aging on CCO₂R in patients during sevoflurane anaesthesia.

Methods

Twenty-four patients were divided into two groups of 12 according to age; 20–40 yr and 50–70 yr. Anaesthesia was induced with 5 mg · kg^?1 thiopentone and maintained with sevoflurane 1.0 to 1.5% (end-tidal) and nitrous oxide 66% in oxygen to maintain anaesthesia. End-tidal CO₂ tension (P_etCO₂) was altered from 20 to 50 mmHg in 5 mmHg steps by changing the respiratory rate. Middle cerebral blood flow velocity (CBFV) and pulsatility index (Pl) were measured by transcranial Doppier (TCD) at each step change in P_etCO2. The CCO₂R was calculated as the change of CBFV per mmHg at each 5 mmHg interval.

Results

In each group, there were no changes in blood pressure, heart rate, end-tidal sevoflurane concentration, or Pl as the P_ETCO₂ was increased from 20 to 50 mmHg. The CCO₂R at P_ETCO₂ of 35 to 50 mmHg in the younger group (0.80 ± 0.27 (SD) cm·sec^?1·mrnHg^?1) was larger than that in the elderly group (0.31 ± 0.16 cm · sec^?1 mmHg^?1)(P< 0.0l).

Conclusion

It is concluded that, during sevoflurane anaesthesia. CCO₂R is well preserved, and that the CCO₂R at P_ETCO₂ of 35 to 50 mmHg in the 20 to 40 yr age group is greater than that in the 50 to 70 yr age group.     

The effects of acute proximal basilar artery occlusion on the primate cerebral circulation

Summary The effects of acute proximal basilar artery occlusion on blood flow, autoregulation and CO₂ reactivity in four separate regions of the brain (cerebral cortex, thalamus, brainstem and caudal pons) were studied and compared in 30 anaesthetised baboons. Significant flow changes were seen in all areas of the basilar territory, even in instances where the posterior communicating artery was observed to be relatively large. Flow changes were also seen in regions of the brain remote from the basilar territory. Areas furthest from the collateral blood supply showed the largest changes in blood flow, as has previously been shown in the case of proximal middle cerebral artery occlusion. From this, one can predict that in surgery, the more rostral the occlusion of the artery, the safer the procedure should be. At normal blood pressure, while the collateral circulation to the brainstem and thalamus was adequate to maintain normal electrical function after basilar occlusion, the flow was totally inadequate to maintain autoregulation or CO₂ reactivity in the basilar territory.     

Effect of ketanserin on cerebral blood flow autoregulation in healthy volunteers

Summary The effect of a clinically relevant dose of ketanserin (10 mg as a bolus followed by an infusion of 6mg/h) on cerebral blood flow (CBF) and CBF autoregulation was examined in 12 healthy volunteers. Changes in CBF were estimated by the cerebral arteriovenous-oxygen saturation difference method, while mean arterial blood pressure (MABP) was increased by norepinephrine and decreased by ganglionic blockade (trimethaphan camphosulphonate) combined with lower body negative pressure one hour after the infusion of ketanserin. During ketanserin infusion, MABP fell insignificantly by 2.5 mmHg (6 to –2), while CBF rose insignificantly by 5 ml/100 g/min. Autoregulation was preserved in all volunteers. CO₂-correction factors from 0 to 4.6% CBF/0.1 kPa were used. The lower limit of CBF autoregulation was 82 mmHg (80–86) with an SE of 3 mmHg (1–5) similar to a previous control group of healthy volunteers. Aside from a major decrease in MABP in one subject, no adverse side effects were observed.The present study shows that CBF autoregulation is maintained during ketanserin infusion.     

The effect of changes in arterial CO2 tension on plasma lidocaine concentration

The authors studied the effect of changes in arterial carbon dioxide tension on plasma tidocaine concentrations during a constant lidocaine infusion in eight healthy volunteers. With a PaCO₂ of 41.4 ±. 0.9mmHg (mean ± SE), total plasma lidocaine concentrations were 3.97 ± 0.20 μg·ml^-1. There was no significant change associated with hypercarbia (PaCO₂ = 55.7 ± 1.5mmHg, lidocaine = 3.93 ± 0.18 μg±ml^-1)or hypocarbia (PaCO₂ = 19.5 ± 1.4mmHg, lidocaine = 4.29 ± 0.25 μg·ml^-1), despite the known effects of changes in CO₂ tension on hepatic blood flow and lidocaine protein binding. During hypercarbia, plasma lidocaine binding decreases while total plasma lidocaine remains essentially constant; therefore, increased CO₂ tensions could cause toxicity if total lidocaine concentrations were in the high therapeutic range (5 μg·ml^-1). Four subjects experienced transient symptoms of mild lidocaine toxicity during acute increases in carbon dioxide tension.     

CO2 reactivity in patients after subarachnoid haemorrhage

Summary CO₂ reactivity was tested in patients with transcranial Doppler sonography (TCD) and endtidal CO₂ measurements after an average time interval of ten months after subarachnoid haemorrhage (SAH). After deliberately changing breathing there was a significant change in endtidal CO₂ and in flow velocities in all three examination groups. Comparing 27 patients with SAH and 5 patients treated for incidential aneurysms and 20 patients without cerebrovascular disease there were no significant differences in CO₂ reactivity. Furthermore, there were no right to left differences. In 12 patients with vasospasm, two of them treated by percutaneous transluminal angioplasty for delayed ischaemic deficits, CO₂ reactivity was normal at the time of investigation. Furthermore, normal CO₂ reactivity was found in patients after SAH and surgery for ruptured aneurysms regardless of the severity of the SAH.     

Measurements of CO2 reactivity and barbiturate reactivity in patients with severe head injury

Summary In nine patients with severe head injury subjected to continuous hyperventilation and barbiturate coma treatment with pentobarbitone, the regional cerebral blood flow was measured as initial slope index (ISI) with a 32 channel Cerebrograph, and cerebral metabolic rate of oxygen (CMRO₂) was calculated as the product of mean global CBF and the arterio-venous oxygen content difference.CBF was measured at strategic intervals either to follow the treatment (hyperventilation and/or pentobarbitone), or to determine whether these principles of treatment should be intensified or reduced. During the flow measurements the CO₂ reactivity and the reactivity to a bolus injection of thiopentone 5 mg/kg were calculated globally and regionally. The global CO₂ reactivity was calculated as relative (%change CBF/PaCO₂ mmHg) and absolute (CBF/ PaCO₂ mmHg), and the reactivity to barbiturate was calculated globally as CMRO₂, and regionally as %change rCBF.The absolute and relative global CO₂ reactivities correlated positively with the mean. CBF values before hyperventilation, and the global barbiturate reactivity was dependent on the CMRO₂ value obtained before hyperventilation. However, at low levels of CMRO₂ ranging between 1.0 and 1.1 ml O₂ the barbiturate reactivity was abolished. The regional studies of CBF, CMRO₂, CO₂ reactivity and barbiturate reactivity gave important information, when decisions concerning therapeutic regimes with special reference to hyperventilation and sedation with pentobarbitone were necessary.     

Local cortical cerebral blood flow and response to carbon dioxide during anesthesia in patients with moyamoya disease

Purpose. The CO₂ reactivity of cortical cerebral vessels and local cortical blood flow (l-CoBF) were evaluated during anesthesia in patients with moyamoya disease who were undergoing revascularization surgery. Methods. Using laser–Doppler flowmetry, the CO₂ reactivity of cortical cerebral vessels and l-CoBF were measured continuously in five patients at the local surgical field of the middle cerebral artery (MCA) territory. Results. Local-CoBF values obtained during the normocapnic condition varied from site to site of gyrus in the MCA region (0–73 ml · 100 g⁻¹·min⁻¹). Local-CoBF was maximal at 39–43 mmHg of the PaCO₂ range, and decreased above and below this range. The response of l-CoBF to CO₂ was larger at the sites where the maximal level was obtained during normocapnia. In two patients, l-CoBF decreased by about 50%, and remained law even 40 min after administration of acetazolamide. Conclusion. In patients with moyamoya disease, l-CoBF values obtained during the normocapnic condition varied from site to site of gyrus, and not only hypocapnia but also hypercapnia decreased l-CoBF within the MCA region. Received for publication on May 29, 1998; accepted on January 26, 1999     

Brain oxygen monitoring: in-vitro accuracy,long-term drift and response-time of Licox- and Neurotrend sensors

Summary Background. Oxygen tension sensors have been used to monitor tissue oxygenation in human brain for several years. The working principals of the most frequently used sensors, the Licox (LX) and Neurotrend (NT), are different, and they have never been validated independently for correct measurement in vitro. Therefore, we tried to clarify if the two currently available sensors provide sufficient accuracy and stability.Method. 12 LX oxygen tension sensors and NT sensors were placed into a liquid-filled tonometer chamber. The solution was kept at 37 ± 0.2 °C and equilibrated with five calibration gases containing different O₂- and CO₂-concentrations. After equilibration, readings were taken for each gas concentration (accuracy test). Afterwards, the sensors were left in 3% O₂ and 9% CO₂ and readings were taken after 24, 48, 72, 96 and 120 hours (drift test). Thereafter, a 90% response time test was performed transferring sensors from 1% to 5% oxygen concentration and back, using pre-equilibrated tonometers.Findings. All Licox oxygen probes [12] were used for this study. Two of 14 Neurotrend sensors did not calibrate, revealing a failure rate of 14% for NT. Oxygen tension during the accuracy test was measured as follows: 1% O₂ (7.1 mmHg): LX 6.5 ± 0.4, NT 5.3 ± 2.3 mmHg, 2% O₂ (14.2 mmHg): LX 12.9 ± 0.6, NT 12.1 ± 2.2 mmHg, 3% O₂ (21.4 mmHg): LX 19.8 ± 0.7, NT 19.4 ± 2.4 mmHg, 5% O₂ (35.8 mmHg): LX 33.4 ± 1.0 mmHg, NT 33.5 ± 2.9 mmHg, 8% O₂ (57.0 mmHg): 53.8 ± 1.5, NT 53.6 ± 3.3 mmHg. After 120 hours in 3% O₂ (21 mmHg), LX measured 19.8 ± 1.9 mmHg, NT 17.9 ± 4.7 mmHg. 90% response time from 1% to 5%/5% to 1% oxygen concentration was 129 ± 27/174 ± 26  sec for LX, 55 ± 19/98 ± 39 sec for NT.Conclusions. Both systems are measuring oxygen tension sufficiently, but more accurately with LX probes. NT sensors read significantly lower pO₂ in 1% O₂ and show an increasing deviation with higher oxygen concentrations which was due to two of twelve probes. A slight drift towards lower oxygen tension readings for both sensors but more pronounced for the NT does not impair long-term use. NT measures pCO₂ and pH very accurately.     

Cuffed oropharyngeal airway and capnometry: comparison of end-tidal and arterial carbon dioxide pressures

Purpose. The aim of this study was to investigate the reliability of end-tidal CO₂ tension (PetCO₂) as a predictor of PaCO₂ during anesthesia in patients breathing spontaneously via a cuffed oropharyngeal airway (COPA). Methods. Twenty adult patients scheduled for minor sur-gery were included in this study. After propofol injection, an appropriate size of COPA was inserted. Anesthesia was maintained with 60% nitrous oxide in oxygen (total flow rate of 5 l·min⁻¹) supplemented with propofol infusion. The patients were allowed to breathe spontaneously throughout the procedure. PaCO₂ and PetCO₂ were simultaneously measured when a steady state of anesthesia was reached. Results. PaCO₂ (48.8 ± 5.4 mmHg, range 36.2–58.0 mmHg) was higher than PetCO₂ (43.1 ± 4.2 mmHg, range 32–51 mmHg) in all patients. The difference between end-tidal and arterial CO₂ tension was 5.7 ± 3.2 mmHg (range 0.5–13.0 mmHg), and was significantly correlated with PaCO₂ (P < 0.01). Conclusion. The results of this study suggest that PetCO₂ in anesthetized patients breathing spontaneously through a COPA is sometimes unreliable as an indicator of PaCO₂ level, and there is some possibility of unexpected hypercapnia. Received for publication on August 31, 1998; accepted on February 9, 1999     

Gender differences in cerebrovascular reactivity to carbon dioxide during sevoflurane anesthesia in children: preliminary findings

Background: Cerebrovascular reactivity to carbon dioxide (CO₂R) is affected by age, gender and anesthetic agents. While gender differences in CO₂R are described in adults, there are no such data in children. Aim: To examine the gender differences in CO₂R in children during sevoflurane anesthesia. Methods: Five girls and five boys <15 years of age and ASA physical status I, undergoing general anesthesia for elective surgery were enrolled. Under steady‐state anesthesia with <1.0 MAC sevoflurane, middle cerebral artery blood flow velocity changes were monitored using Transcranial Doppler ultrasound while endtidal carbon dioxide (EtCO₂) was adjusted from 40 to 30 mmHg (hypocapnia) and then from 40 to 50 mmHg (hypercapnia). CO₂R was calculated between EtCO₂ ranges 30–40 and 40–50 mmHg. Cerebrovascular resistance (eCVR) was estimated as MAP/Vmca and the change in eCVR (ΔeCVR) between EtCO₂ 30 and 40 mmHg and between EtCO₂ 40 and 50 mmHg was calculated. Results: There was no gender difference in CO₂R. However, both CO₂R and ΔeCVR were lower in the EtCO₂ 40–50 mmHg range compared to EtCO₂ 30–40 mmHg range only in girls (P = 0.01 and P = 0.01, respectively). Vmca increased significantly with increase in CO₂ (P < 0.001) for both boys and girls. The coefficient of nonlinear correlation (r) between Vmca and EtCO₂ was 0.88 in girls vs 0.66 in boys. Conclusion: While there were no gender differences in CO₂R within the individual EtCO₂ ranges examined, girls but not boys had a significantly lower CO₂R and ΔeCVR in the higher EtCO₂ range during <1.0 MAC sevoflurane anesthesia.     

Effect of controlled blood pressure increase on cerebral blood flow velocity and oxygenation in patients with subarachnoid haemorrhage

Background

Patients with aneurysmal subarachnoid haemorrhage (SAH) might have impaired cerebral autoregulation, that is, CBF – and thereby oxygen delivery – passively increase with an increase in CPP. This physiological study aimed to investigate the cerebral haemodynamic effects of controlled blood pressure increase in the early phase after SAH before any signs of delayed cerebral ischaemia (DCI) occurred.

Methods

The study was carried out within 5 days after ictus. Data were recorded at baseline and after 20 min of noradrenaline infusion to increase mean arterial blood pressure (MAP) by a maximum of 30 mmHg and to an absolute level of no more than 130 mmHg. The primary outcome was the difference in middle cerebral artery blood flow velocity (MCAv) measured by transcranial Doppler (TCD), while differences in intracranial pressure (ICP), brain tissue oxygen tension (PbtO₂), and microdialysis markers of cerebral oxidative metabolism and cell injury were assessed as exploratory outcomes. Data were analysed using Wilcoxon signed-rank test with correction for multiplicity for the exploratory outcomes using the Benjamini-Hochberg correction.

Results

Thirty-six participants underwent the intervention 4 (median, IQR: 3–4.75) days after ictus. MAP was increased from 82 (IQR: 76–85) to 95 (IQR: 88–98) mmHg (p-value: <.001). MCAv remained stable (baseline, median 57, IQR: 46–70 cm/s; controlled blood pressure increase, median: 55, IQR: 48–71 cm/s; p-value: .054), whereas PbtO₂ increased significantly (baseline, median: 24, 95%CI: 19–31 mmHg; controlled blood pressure increase, median: 27, 95%CI: 24–33 mmHg; p-value <.001). The remaining exploratory outcomes were unchanged.

Conclusion

In this study of patients with SAH, MCAv was not significantly affected by a brief course of controlled blood pressure increase; despite this, PbtO₂ increased. This suggests that autoregulation might not be impaired in these patients or other mechanisms could mediate the increase in brain oxygenation. Alternatively, a CBF increase did occur that, in turn, increased cerebral oxygenation, but was not detected by TCD. Trial registration: clinicaltrials.gov (NCT03987139; 14 June 2019).     

The effects of indomethacin on intracranial pressure,cerebral blood flow and cerebral metabolism in patients with severe head injury and intracranial hypertension

Summary In five head-injured patients with cerebral contusion and oedema in whom it was not possible to control intracranial pressure (ICP) (ICP>20 mmHg) by artificial hyperventilation (PaCO₂ level 3.5–4.0 kPa) and barbiturate sedation, indomethacin was used as a vasoconstrictor drug. In all patients, indomethacin (a bolus injection of 30 mg, followed by 30 mg/h for seven hours) reduced ICP below 20 mmHg for several hours. Studies of cerebral circulation and metabolism during indomethacin treatment showed a decrease in CBF at 2h. After 7h, ICP remained below 20 mmHg in three patients, and these still had reduced CBF. In the other patients a return of ICP and CBF to pretreatment levels was observed. In all patients indomethacin treatment was followed by a fall in rectal temperature. These results suggest that indomethacin due to its cerebral vasoconstrictor and antipyretic effect should be considered as an alternative for treatment of ICP-hypertension in head-injured patients.Presented at the Fifth Nordic CBF Symposium, Lund, Sweden, 21–22 May 1990.