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Table 4.3.Intraoperative non invasive TCD during pneumoperitoneum
Kim et al., 2014 et al., 2014 Verdonck Whiteley et al.,2014 (children) Min 2015
Number of patients 20 20 25 25
race NA NA 80% white 20% African
NA BMI (kg/m2) mean±sd (range) 24,2±5,9,(20,7-31,25) 26,6 (3,7) 28,4±3.4(23,9-37,8) 15,9±1,7
sex distribution (%male) 100% 100% 100% 48%M/52%F
age (years)
mean 64,9 63 62,2 53,1 months
sd 6,8 NA 6 23,3
range 50-75 50-82 51-74 NA
median 66 NA NA
ASA score (range) 1 to 3 1 to 2 2 (56%), 3(44%) NA
type of procedure(s) RALRP RARLP RALRP Not specified
duration of surgery (minutes) mean 141 NA 372,9 50,8 sd 40,7 NA 98,5 11,3 median 137,5 NA NA NA range 90-223 NA 240-658 NA duration of pneumoperitoneum (minutes) NA NA NA 31,7 mean NA NA NA sd NA NA NA 10,5 duration of Trendelemburg (minutes) NA 213 NA NA mean 106,5 58 NA NA sd 38,5 NA NA NA median 100 NA NA NA Range 62-180 NA NA NA IAP(mmHg) NA NA NA 10
PaCO2 (mmHg)in relation
to PP incr.signif. Incr. Signif. NA NA
ETCO2 (mmHg) 35-40 30-40 30-40 35-40
MAP in relation to PP
decreases signif
Incr. signif NA Incr. Signif. Anesthetic drugs desfluorane
remifentanil sevofluorane sulfentanil isofluorane remifentanil sevofluorane OSND (mm) before anesthesia 4,6±0,4 4,9±0,2 4,5±0,05 NA before pneumo 4,8±0,4 4,9±0,3 NA 4.3 ±0.3
100 after pneumo 5,4±0,5 5,0±0,2 NA 4.6 ±0.3 after trend 5,4±0,4 5±0,2 NA NA after procedure 4,8±0,4 4,9±0,2 0,55±0,05 4.3 ± 0.3
PP and Trend influence ONSD* Statist sign Neurol complications Yes P<0.05 No No P>0.05 No Yes ONSD/MAP p=0.048 (CI=0.000-0.045) ONSD/ETCO2 P=0.072 (CI-0.005-0.117) No Yes P<0.05 No No DISCUSSION
Laparoscopy has become the preferred method for surgical treatment of most intra-abdominal pathology, because it is minimally invasive and because it reduces risks of secondary peritoneal adhesions. Intra-abdominal CO2 insufflation, however, is associated with an increase of ICP (16-18). PP can cause compression of vena cava with a consequent increase and obstruction of cerebral venous outflow (16,17). Nausea, headache and other clinical symptoms that could be associated with increased ICP have been reported after laparoscopy (19).
During laparoscopy sustained increases in ICP of more than 12 mmHg above the baseline in patients with ventriculo-peritoneal shunts have been reported (16).
Animal models showed that ICP increases significantly above 15 mmHg of IAP, reaching 150 % over control values with intra-abdominal pressures above 16 mm Hg during Trendelenburg (17).
This preliminary evidence indicated that in patients at risk of developing an increased ICP as a result of head injury or of space occupying lesions, peritoneal insufflation could induce abrupt intracranial hypertension and should probably be used with special caution and close monitoring (21).
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Invasive methods are still the gold standard in the measurement of ICP, but they are associated with major complications (22,23,1,6,24).
Several techniques have been proposed for the non-invasive measurement of ICP (25-27). Among these we selected PI and FVdICP obtained by TCD and the ONSD ultrasound. TCD is a non-invasive method for the measurement of middle cerebral artery (MCA) blood flow velocity commonly used in standard care of neurocritical care patients. PI has been the most commonly used formula (28-33), but many studies have demonstrated that this measure cannot estimate ICP values with reliable precision (34,32,33).
Schmitd, Czosnyka et al. (8) proposed a new method for estimation of CPP based on FVd and demonstrated that the absolute difference between real CPP and non-invasive Cerebral Perfusion Pressure (nCPP) calculated with this new method was very small.
Effects of PP on TCD derived PI have been studied in adults and children (see table 4.2) with discordant results as concerns the interaction between Flow Velocities (FV) and PP, some considering also the possible role of Trendelenburg position.
The two reports with TCD assessment during PP (14,15) which were about two patients with intracranial disease, concluded that TCD, being a safe technique that can detect minimal variations of cerebral hemodynamics, could be a valid monitoring option for patients undergoing laparoscopic procedures with preexisting intracranial pathology. Several studies on adults (35,20,36-39) and children (40,41) included a wider number of patients (20,36) undergoing different laparoscopic procedures requiring (35-37,39) or not (35,20) Trendelenburg position and monitored with TCD. Among these studies TCD measurement methods, IAP parameters, ventilator settings (including ETCO2), patients number, characteristics and anesthesiological management are comparable. A mixed anesthesia with sevoflurane or isoflurane was used in all cases in a window of 0.5-1.5 mean alveolar concentration (MAC) (42) and it is well known that at these levels neither isoflurane nor sevoflurane do not induce any significant dose-related changes of blood flow velocities (43) nor changes of cerebral blood flow autoregulation (44).
Despite this, results concerning effects of PP on FV and PI are discordant: PCO2 tends always to increase after PP, but not all authors observed a concomitant increase of FV
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(35,36).
PI seems not to be significantly influenced by PP and head down position in most of the described papers. Surprisingly, one study on a paediatric cohort, registered a decrease of PI during PP (40).
Thus, the available literature seems not to clarify whether PI derived from TCD could be a reliable measure to monitor ICP patients during laparoscopy.
In our case report, PI reached a maximum value of 1.12 after PP induction, which would not associate to significant ICP increase (28-33). To our knowledge FVdICP formula has never been used to assess nICP intraoperatively. In our case report, nICP obtained with this new method indicated an ICP of 26 mmHg during PP (with preoperative ICP values of 16 mmHg), which recovered after PP desufflation.
Optic nerve sheath diameter (ONSD) measures have shown to be well correlated to ICP (45,46).
The optic nerve sheath is in continuity with the meninges of the central nervous system. During intracranial hypertension, compensatory mechanisms such as intra-cerebral blood and cerebrospinal fluid (CSF) shifts occur. As CSF is incompressible, ICP is directly transmitted to the fluid in the optic nerve sheath, increasing its diameter. According to human studies, this phenomenon occurs within minutes of acute changes in ICP (13,47,10). Cutoff values of 5.7 or 5.8 mm are used to predict elevated ICP (≥ or >20 mmHg) (48,46,49). ONSD is a safe, repeatable technique, and has a fast learning curve: novice sonologists need only 25 scans to obtain adequate results (45). ONSD behavior during PP has been investigated only in three recent studies on adults (50-52), and one in children (42), where patients without intracranial pathologies underwent laparoscopy with prolonged PP and Trendelenburg positioning.
Despite similar general patient type, intra-procedural conditions (included type of anesthesia) among these ONSD studies, which are also well comparable to those in the TCD studies in adults, the conclusions were quite different: three out of four OSND studies (51,52,42) detected increased ICP (reaching values above 20 mmHg) during PP and in particular Trendelenburg; whereas in TCD studies PI did not detect significant ICP changes
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in similar conditions.
Moreover, we observed that in all the studies the PCO2 levels did not exceed the cut-off value for impaired autoregulation (53).
All the described studies involved patients not affected by intracranial pathology and show contrasting results, though even in those cases where an increased ICP was detected, no neurological sequels were observed. The currently available literature lacks contingency analyses which are necessary to be considered in future studies.
All in all, the present review indicates that ONSD might be sensitive to IAP variations, whereas TCD derived PI is not, though comparative studies are missing. In our case report, the patient was affected by a GBM with mass effect. In this patient, mean ONSD before PP was 5,5 mm, that is close to the threshold considered at risk of increased ICP (5,7-5,8 mm). After CO2 insufflation for PP, mean ONSD significantly increased up to 6,8 mm, that is associated to an ICP above 20 mmHg, which recovered to baseline diameter after PP desufflation. This can be explained by the fact that in the presence of space occupying lesions the compensation mechanisms that normally may attenuate intracranial effects induced by PP (54) are exhausted, as previously described (55).
On TCD measurements, PI values were always stable (0.91-1.1), whereas FVdICP measures reached a value of 26 mmHg of ICP after PP insufflation, decreasing at the end of the procedure.
To our knowledge, a combination of ONSD measurements and TCD has never been applied intraoperatively. Moreover, FVdICP formula has never been used as intraoperative monitoring. The present case shows that nICP measured through FVd formula and ONSD provided concordant information. Many authors demonstrated that FVd formula and ONSD have a strong correlation with ICP invasively measured (8-14).
This can increase the likelihood that our intraoperative measures were relieable, even though not compared with an invasive gold standard. Moreover, the utility of PI is controversial (33).
In our reported case nICP values were not followed by anaesthesiological countermeasures for two reasons: first of all, values peaked immediately after PP induction (T1) and tended
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to decrease after 30 minutes (T2); second, at this point the surgical procedure was concluded and after PP desufflation (T3) ONSD and FVdICP were normalized. The availability of nICP measure could allow to timely apply intraoperatively anaesthesiological measures to control ICP such as slight hyperventilation or osmotic therapy or even to suggest a switch to open surgery if ICP levels are persistently elevated. Certainly, a continuous form of intraoperative monitoring would even be preferable, since in TCD the isolated measurement is less reliable than the observation of trends and average values (32,33,34). Finally, larger observational trials are required to obtain some measure of sensitivity, specificity, and avoid false reporting. Once better contingency and outcome data become available, the possible routinary use of these non-invasive ICP assessment methods might be considered.
CONCLUSIONS
Noninvasive ICP monitoring could be useful in situations at risk of intracranial hypertension, such as PP, especially where invasive ICP monitoring is not indicated or available.
TCD derived formulae, in particular FVd, and ONSD ultrasound are non-invasive, safe techniques, which correlate with ICP and may provide some useful information in patients with preexisting intracranial diseases undergoing laparoscopic procedures. Further, observational/contingency based trials and controlled studies aimed at comparing these methods with the invasive gold standard are necessary to validate this theory and also necessary to appropriately interpret related information.
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Chapter 5 . Effects of prone position and positive end expiratory
pressure on non-invasive estimators of ICP
Chiara Robba, Nicola Bragazzi, Alessandro Bertuccio, Danilo Cardim, Joseph
Donnelly, Mypinder Sekhon, Andrea Lavinio, Derek Duane, Rowan
Burnstein, Basil Matta, Susanna Bacigaluppi, Marco Lattuada, and Marek
Czosnyka
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ABSTRACT
Background: Prone positioning and positive end expiratory pressure (PEEP) can improve pulmonary gas exchange and respiratory mechanics. However, they may be associated with the development of intracranial hypertension. Intracranial Pressure (ICP) can be non-invasively estimated from the sonographic measurement of the optic nerve sheath diameter (ONSD) and from the Transcranial Doppler analysis of the pulsatility (ICPPI) and the diastolic component (ICPFVd) of the velocity waveform.
Methods: The effect of the prone positioning and PEEP on ONSD, ICPFVd, and ICPPI was assessed in a prospective study of 30 patients undergoing spine surgery. One-way repeated measures analysis of variance, fixed-effect multivariate regression models and receiver operating characteristic analyses were used to analyse numerical data.
Results: The mean values of ONSD, ICPFVd and ICPPI significantly increased after change from supine to prone position. Receiver operating characteristic analyses demonstrated that, among the non-invasive methods, the mean ONSD measure had the greatest area under the curve signifying it is the most effective in distinguishing a hypothetical change in ICP between supine and prone positioning (0.86±0.034 [0.79 to 0.92]). A cutoff of 0.43 cm was found to be a best separator of ONSD value between supine and prone with a specificity of 75.0 and a sensitivity of 86.7.
Conclusions: Non-invasive ICP estimation may be useful in patients at risk of developing intracranial hypertension who require prone positioning.
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INTRODUCTION
Mechanical ventilation in the prone position and the use of positive end expiratory pressure (PEEP) are frequently used techniques which improve oxygenation in patients at risk of respiratory failure (1,2). Prone positioning improves oxygenation in patients with acute lung injury and acute respiratory distress syndrome by reducing ventilation–perfusion mismatch (3-5). PEEP improves oxygenation by opening collapsed alveoli (6) and mitigates end-expiratory alveolar collapse during general anesthesia, reduces intrapulmonary shunt, increases functional residual capacity, and allegedly reduces the incidence of ventilator-associated pneumonia and lung injury (2, 7).
However, both prone positioning and PEEP can have undesirable effects on cerebral physiology. Prone positioning can increase intracranial pressure (ICP) in patients with intracranial pathology by impairing jugular venous outflow (8, 9). PEEP, by increasing central venous pressure (CVP) and by impeding cerebral venous return to the right atrium, can increase ICP and decrease mean arterial pressure, both resulting in decreased cerebral perfusion pressure (CPP) (10, 11). Consequently, in acutely brain injured patients, ventilation goals are often in conflict with ICP control strategies (12).
The gold standard technique for ICP measurement is an intraventricular catheter (13), however this method is invasive and can have complications (14, 15). Non-invasive ICP (nICP) measurement is a promising technique, still under development in adult (16, 17) and pediatric population (18).Optic nerve sheath diameter (ONSD) measurement using ocular ultrasonography is a safe, quick, reliable and reproducible technique for the assessment of ICP (19, 20 21). Transcranial Doppler Ultrasonography (TCD) can also non-invasively assess ICP and CPP. Increased ICP produces characteristic changes in cerebral blood flow velocity (FV) waveform that can be assessed by decreases in the diastolic FV and increases in the pulsatility index (PI=systolic FV – diastolic FV) / mean FV) (22) and several methods TCD derived have been proposed to assess non-invasively ICP, showing good performance (23, 24).
Therefore, in patients without invasive ICP monitoring, nICP methods may be useful for determining whether PEEP or prone positioning is causing a pathological increase in ICP. In this study, we compared 3 different non-invasive ICP estimation techniques to investigate the effect of prone position or PEEP on these estimators in non-brain injured
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patients compared to supine position or non-PEEP status, respectively.
METHODS
The study was approved by the institutional ethics committee at Galliera Hospital, Genova, Italy and, before enrolment, written informed consent was obtained from all participants. Exclusion criteria were: age < 18 years, pre-existing ophthalmic diseases or a history of ophthalmic surgery, and pre-existing neurological disease. A total of thirty-three adult patients between May 2015 and July 2015 who were American Society of Anesthesiologists (ASA) class I to II scheduled for elective spine surgery were included in this study. Of these, three patients were excluded because it was not possible to obtain a suitable ultrasound temporal window in the operating room.
On arrival in the operating room, standard monitoring was applied, including electrocardiography, pulse oximetry, and non-invasive arterial blood pressure. The participants were pre-medicated with midazolam (0.05 mg/kg). General anesthesia was induced with propofol 1.5 mg/kg, and fentanyl 1 µg/kg. Cisatracurium besilate 0.15 mg/kg was administered intravenously to facilitate oro-tracheal intubation. After tracheal intubation, mechanical ventilation was performed with a tidal volume of 8 mL/kg and respiratory rate was adjusted to maintain an end-tidal carbon dioxide (EtCO2) of 35 to 40 mm Hg during surgery. Anesthesia was maintained with remifentanil 0.05 to 0.2 µg/kg/min and 1 to 1.5 minimum alveolar concentration (MAC) of sevofluorane in 50% oxygen/air.
Patients were carefully turned from the supine to prone position by a team of five staff members (three staff nurses and two physicians); two on each side, one controlling the legs and feet and one (the anaesthetist) controlling head and airways and coordinating the procedure.
In the prone position, we limited the shoulder abduction to less than 90° to avoid overstretching of the brachial plexus. We placed the forearm in a neutral position to minimize the direct pressure on the ulnar nerve at the elbow and applied soft padding under the elbows, chest and pelvis. The potential for increased intrathoracic pressure
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caused by the increased abdominal pressure in prone position was minimized by using foam padding to limit abdominal compression. The head was put in neutral position on an open soft head ring (Horseshoe Head Pad - High - Adult Size) to avoid any direct pressure to the eyes, nose, and mouth.
Ultrasonographic measurement of ONSD was conducted by a single trained investigator (CR) with more than 30 ultrasound examinations of experience, as described in previous studies (25).
A linear 7.5 MHz ultrasound probe (7L4a, Mindray Medica Dc-n3) was carefully placed on the closed upper eyelid without exerting pressure on the eye, in the supine and prone positions. In the two-dimensional mode, ONSD was measured 3 mm behind the globe using an electronic caliper. The ONSD measurement in the prone position was performed by one operator (C.R) while an assistant held the head rotated 30 degrees rightward (to measure the right ONSD) and then 30 degrees leftward (to measure the left ONSD). Two measurements were performed for each optic nerve, one in the transverse plane and one in the sagittal plane. The final ONSD was taken as the mean of the four values measured in both eyes of each patient.
In the supine and prone position, the temporal windows are easily accessible. The middle cerebral artery flow velocity (FV) of both sides was determined by Transcranial Doppler using a 2.5 MHz ultrasound probe (2P2, Mindray Medica Dc-n3), and the final FV measurement corresponded to the average of the two values of both sides. In addition, we assessed the duration of surgery, of anesthesia, the amount of intraoperative blood loss, and the volume of administered fluids.
Mean arterial pressure (ABPm), heart rate (HR), Airways Peak Pressure (Ppeak), Airways Plateau Pressure (Pplat), End Tidal CO2 (ETCO2), middle cerebral artery flow velocities (systolic (FVs), mean (FVm), and diastolic (FVd)) by TCD, and ONSD were recorded at the following time points:
T0: baseline, at least 10 minutes after induction of anaesthesia, in supine position and PEEP=0;
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T1: after 10 minutes of prone position ventilation, at zero end expiratory pressure (ZEEP), PEEP=0;
T2: in prone position, after slow and gradual (2 cmH20 every minute) application of PEEP=8 cmH20, after 10 minutes of PEEP=8 cmH20;
T3: at the end of surgery, after 10 minutes of supine position, with PEEP=8 cmH20, without disconnection of ventilation while returning to supine position.
PI was calculated according to the method of Gosling (26): PI= (FVs-FVd)/FVm;
nICP derived by PI (PIICP) was calculated according to a formula based on data described by Budohoski et al. (27).
ICPPI=4.47·PI+12.68.
According to Czosnyka et al.(28), non-invasive cerebral perfusion pressure (nCPP) has been calculated as:
nCPP=ABPm·FVd/FVm+14
Finally, ICP was then estimated as the difference between inflow (ABPm) and CPP: ICPFVd = ABPm- nCPP= ABPm(1-Fvd/Fvm)-14.
STATISTICAL ANALYSIS
Continuous variables were expressed as mean±SD or median (interquartile range). Categorical variables were expressed as number (percentage). First, data were checked for normality using the D'Agostino-Pearson omnibus test, since it is one of the most powerful and versatile tests for verifying and quantifying how far the distribution of our sample is from Gaussian in terms of asymmetry and shape, and whether these discrepancies are statistically significant. Then Mauchly’s Sphericity Test (29) was performed to control data
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for the sphericity assumption, that is to verify whether the variances of the differences between all possible combinations or pairs of groups (or said otherwise all the possible levels of the independent variable) are equal. In case of sphericity violation, data were corrected using the Greenhouse-Geisser correction or the Huynh-Feldt correction, according to the value of the epsilon. If the epsilon was less than 0.75, the first approach was used.
One-way repeated measures analysis of variance (rmANOVA) was used to evaluate the effect of the different time points on the ONSD, ICPPI, ICPFvd, PI, FVs, FVd, FVm, nCPP, ABPm HR, ETCO2, Ppeak, and Pplat values. This analysis was used since rmANOVA (known also as within-subjects ANOVA or ANOVA for correlated samples) is the equivalent of one-way ANOVA, in case of related, not independent groups, as for our sample. The impact of the different time-points was estimated with the Pillai’s trace, the Wilks’ lambda, the Hotelling- Lawley’s trace and the Roy’s largest root, together with the F-statistics. If the impact of the anesthesiological time-points were significant, Sidak’s post hoc analyses were performed, since they are very powerful in correcting for multiple comparisons (30). Partial η2 was computed as a measure of effect-size and was interpreted with the Cohen’s rule of thumb: small if in the range 0.02-0.13, medium if in the range 0.13-0.26, and large if >0.26. Observed statistical power was also calculated.
A generalized fixed effects regression model with repeated measures was used to estimate and compare the impact of the studied variables on the different estimates of ICP, adjusting for confounding parameters. This statistical technique enables to represent the observed quantities in terms of explanatory variables that are treated as if the quantities were non-random. This technique was chosen because of the small number of patients recruited and because each measurement was made by only one operator. For this reason, the data were treated as a pilot study modeling fixed patient effects. In other words, findings comparing patients should be intended to apply only to the specific patients in the study, without making any inference to hypothetical populations of patients and operators in the way that a random-effects model could have done in a larger study.
A two-way ANOVA, an extension of one-way ANOVA, was performed because this technique enables to assess the influence of two different categorical independent variables
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on one continuous dependent variable and whether there is any significant interaction between them. In our case, it was performed in order to assess the effect of body position (supine versus prone) and PEEP on the different non-invasive ICP estimates.
Receiver operating characteristic (ROC) analyses were performed, enabling a comparison ability of the different nICP estimators to capture potential changes of ICP during different anesthesia time-points. It is important to emphasize that in this study we did not compare the nICP estimators against a gold standard invasive ICP, rather, we used ROC analyses to see which nICP estimator was best able to distinguish between baseline and prone positioning or baseline and PEEP. Cutoff values were chosen using the Youden index, the most used criterion which tends to maximize the correct classification rate, besides being relatively easy to compute.
A p-value <0.05 was considered statistically significant. All statistical analyses were performed using commercial statistical software, namely MedCalc Statistical Software version 15.4 (MedCalc Software bvba, Ostend, Belgium; https://www.medcalc.org; 2015) and IBM SPPS version 22.0.
RESULTS
The study recruited a total of 30 ASA 1-2 participants undergoing spine surgery. None of the patients had known intracranial or ocular pathology. Demographic and surgical data of the patients are shown in table 5.1.
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Table 5.1. Demographic and surgical data of the patients. Sex F/M (n) 13/17 Age (years) 54 ±16.4 (54.5) Weight (kg) 73.8 ± 16.2 (75.0) Comorbilities, n (%): Hypertension asthma COPD
Previous transient ischemic attack Smoker 7 (23.33%) 3 (10%) 2 (6.67%) 1 (3.33%) 3 (10%) Type of surgery n (%): Micro-discectomy Lumbar fixation Laminectomy 16 (53.3%) 7 (23.3%) 7 (23.3%)
Duration of surgery (min) 111.7 ±52 (90.0)
Fluid administration (ml) 1533.3 ± 412.2 (1500.0)
When not specified, values are expressed as mean value ±Standard Deviation (median). Abbreviations: COPD, Chronic Obstructive Pulmonary Disease.
The mean values of HR, ABPm, Ppeak, ETCO2, FVs, FVd, FVm, PI, nCPP, ONSD, ICPFVd and ICP PI at each time point are presented in table 5.2. All the variables apart from ETCO2 showed a significant effect on the different time-points as indicated by a strong observed statistical power and a large partial η2.
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Table 5.2. variation of the different parameters at the different anesthesia timepoints. Parameter Mean T0 (supine) Mean T1 (Prone) Mean T2 (Prone+PEEP) Mean T3 (Supine+PEEP) Parti al η2 Observed power HR 72.93±2.4 8 66.93±2.6 7a 67.48±2.86 78.28±3.05b,c 0.53 0.99 ABPm 79.07±2.9 8 79.67±1.8 7 79.73±2.34 69.27±2.50a,b,c 0.45 0.97 Ppeak 15.83±0.4 0 18.13±0.3 8a 24.10±0.37a,b 20.90±0.57a,b,c 0.95 1.00 Pplateau 11.87±0.4 7 13.83±0.4 5a 17.83±0.45 a,b 15.77±0.44 a,b,c 0.81 1.00 ETCO2 33.60±0.4 2 33.10±0.4 7 32.53±0.43 32.43±0.41 0.16 0.40 FVs 89.80±2.7 5 87.70±2.8 6 86.40±2.60 90.13±2.27c 0.28 0.71 FVd 47.77±1.8 8 38.03±2.0 2a 33.87±2.29a,b 44.03±1.75b,c 0.70 1.00 FVm 61.87±2.0 8 54.53±2.0 8a 51.27±2.11a,b 58.47±2.03c 0.67 1.00 PI 0.68±0.03 0.92±0.05a 1.06±0.07a,b 0.81±0.05c 0.60 1.00 nCPP 71.97±2.6 7 67.87±1.81 65.10±2.25 61.60±2.52 a 0.34 0.84 ONSD 0.40±0.01 0.48±0.01a 0.49±0.01a 0.42±0.01a,b,c 0.92 1.00 ICPFVd 7.07±0.82 11.80±1.4 6a 14.83±1.74a 7.53±0.89b,c 0.43 0.96 ICP PI 15.50±0.1 6 16.67±0.2 3a 17.40±0.31a,b 16.13±0.22a,c 0.64 1.00
Results are given as mean±standard deviation. Partial η2 and observed statistical power are also reported. aStatistically significant compared to T0. bStatistically significant compared to T1. cStatistically significant
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compared to T2. Abbreviations: airways peak pressure (Ppeak), airways plateau pressure (Pplat), End Tidal CO2
(ETCO2), heart rate (HR), intracranial pressure measured through PI (ICPPI) e FVd method (ICPFVd), mean
arterial pressure (ABPm), middle cerebral artery flow velocities (systolic (FVs), mean (FVm), and diastolic (FVd)), non-invasive cerebral perfusion pressure (nCCP), optic nerve sheet diameter (ONSD), pulsatility index (PI), Timepoint (T).
Four patients had a value of ONSD of 0.58 cm or above (the cutoff value for prediction of ICP above 20 mm Hg in previous studies)19 at time-point T2 (in particular, two patients had an ONSD of 0.58 mm and two of 0.60 mm). Among these four patients, three presented a concomitant increased nICP estimates measured with TCD-derived formulae (ICP PI=18, 19, 21 mmHg and ICPFVd 23, 30, 36 mmHg, respectively). No complications (as evaluated with neurological and pupils examination) were observed in any of the enrolled patients.
Compared to baseline values (T0),mean ONSD significantly increased when passing from
supine to prone position (T0-T1; p-value <0.0001), after PEEP=8 application (T0-T2;
p-value <0.0001), and when returning to supine position with PEEP=8 still applied (T0-T3)
(p-value=0.002). ONSD in the prone position with zero PEEP (T1) did not differ from
ONSD in prone position with PEEP (T2) (p-value=0.186) but was significantly higher than
ONSD in supine position with PEEP applied (T3) (T1-T3; p-value <0.0001). ONSD at
T2 was higher than ONSD at time T3 (T2-T3; p-value <0.0001).
Baseline mean value of ICPFVd was significantly lower compared to ICPFVd in the prone
position before (T0-T1; p=0.036), and after prone position plus PEEP application (T0-T2;
p-value =0.001), but not significantly different than ICPFVd in supine position with PEEP still
applied (T0-T3; p-value = 0.998). The application of PEEP in prone position did not affect
mean ICPFVd value (T1-T2; p=0.145), but returning to supine position (T3) had a significant
effect of ICPFVd compared to T2 or T1 (T1-T3; T2-T3; p<0.0001).
Compared to baseline, ICPPI was significantly higher in the prone positions before PEEP (T0-T1; p<0.0001), after PEEP application (T0-T2; p<0.0001), and after returning to supine position with PEEP applied (T0-T3; p=0.040). ICPPI in the prone position without PEEP was significantly lower than after PEEP application (T1-T2; p= 0.024), but not different compared to the supine position with PEEP application (T1-T3; p=0.396). Finally, ICPPI significantly was significantly higher in the prone position with PEEP compared with the
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supine position with maintained PEEP=8 (T2-T3; p=0.001).
The dependence of ONSD, ICPFVd, nCPP and ICPPI on the different anaesthesiological variables is shown in table 3.3. After the corrections of the parameters for confounding factors, ONSD was significantly influenced just by the timepoints. ICPFVd was significantly influenced by FVs.All the nICP methods correlated with each other (p-value <0.0001).
Table 5.3. Fixed effect multivariate regression. Models have been corrected for confounding variables,
namely age, sex, BMI, type and time of surgery, fluids administration, ASA classification and co-morbidities. F-values statistically significant are reported in Bold (p-values).
PARAMETERS PI ONSD FVDIC nCPP ICP-PI
Intercept 0.054 0.169 0.283 0.266 0.000 Timepoint 0.144 0.000 0.364 0.414 0.174 FVd 0.000 0.712 0.267 0.257 0.003 FVm 0.000 0.865 0.064 0.090 0.000 FVs 0.000 0.382 0.002 0.005 0.000 HR 0.954 0.974 0.807 0.730 0.236 ETCO2 0.590 0.989 0.658 0.556 0.499 ABPm 0.798 0.431 0.012 0.000 0.792 Ppeak 0.364 0.154 0.300 0.308 0.693 Pplat 0.535 0.561 0.243 0.335 0.686
Abbreviations: airways peak pressure (Ppeak), airways plateau pressure (Pplat), End Tidal CO2 (ETCO2), heart
rate (HR), intracranial pressure measured through PI (ICPPI) e FVd method (ICPFVd), mean arterial pressure
(ABPm), middle cerebral artery flow velocities (systolic (FVs), mean (FVm), and diastolic (FVd)), non-invasive cerebral perfusion pressure (nCCP), optic nerve sheet diameter (ONSD), pulsatility index (PI).
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The two-way ANOVA describes the effects of prone positioning and PEEP and their interactions on the considered parameters (table 5.4). Our results revealed that body position significantly influenced all the nICP methods, as well as ABPm and HR, airway pressures, and FVd and FVm. PEEP application has a significant effect on hemodynamic (ABPm, nCPP) and respiratory variables (Ppeak and Pplateau), but amongst the nICP estimators it influenced only ICPPI values. Finally, the synergistic action of PEEP and pneumoperitoneum seems to influence just ABPm.
Table 5.4. Two-way ANOVA assessing the effect of PP, PEEP and their interaction on different parameters.
PARAMETER Supine versus prone effect
(p-value)
With PEEP versus without PEEP effect (p-value)
Supine versus prone effect X with PEEP versus without PEEP effect (p-value) ABPm 0.026* 0.049* 0.047* FVd 0<0.001*** 0.050* 0.914 FVm 0.001** 0.111 0.974 FVs 0.269 0.854 0.756 ETCO2 0.646 0.048* 0.491 HR 0.011* 0.253 0.595 PPeak <0.001*** <0.001*** 0.305 PPlat <0.001*** <0.001*** 0.912 PI <0.001*** 0.009** 0.922 ICPFVd <0.001*** 0.177 0.321 ICP IP <0.001*** 0.004** 0.830 Mean ONSD <0.001*** 0.084 0.410 nCPP 0.898 0.006** 0.107
From the ROC analyses, performed to detect changes in body position and of use of non-zero PEEP with nICP estimators, mean ONSD was best able to distinguish between the supine and prone positions (T0-T1; p<0.0001) with an area under the curve (AUC) of 0.864±0.0338 [95% CI 0.789 to 0.920] (Figure 5.1), whilst ROC analysis comparing the
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descriminative ability of nICP methods on detecting increases of PEEP (T2 vs T1), were not performed as no significant effect of PEEP application with ANOVA was found (table 5.2).
Figure 5.1. On the left panel, univariate Receiving Operator Curve (ROC) analysis for the
supination/pronation status the different non-invasive parameters. On the right panel, univariate ROC analysis taking in account the use of PEEP.
ICPPI, ICPFVd, and nCPP presented with an AUC of 0.750±0.0447 [95% CI 0.663 to 0.825], 0.736±0.0454 [95% CI 0.648 to 0.812], 0.694±0.0481 [95% CI 0.603 to 0.774], and 0.502±0.0538 [95% CI 0.409 to 0.594] respectively. Finally, a cut-off of 0.43 cm was found useful to distinguish the mean ONSD value between supine and prone with a specificity of 75.0 and a sensitivity of 86.7 (figure 5.2).
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Figure 5.2. Cutoff value for mean ONSD to distinguish the mean ONSD value between supine and prone.
The method showed a specificity of 75.0 and a sensitivity of 86.7 0, supine without PEEP; 1, prone without PEEP.
DISCUSSION
Our study demonstrates a moderate increase in non-invasive estimators of ICP in patients undergoing spine surgery, as assessed by ONSD- and TCD- based techniques. Changes in position from supine to prone caused a consistent increase in nICP estimators, with ONSD being the most sensitive. Application of PEEP (8 cmH20) seemed to increase the nICPPI but not the other estimators of ICP.Prone positioning and PEEP can be risk factors for the development of increased ICP. However, direct ICP monitoring is invasive and carries risks. Thus, its use in elective procedures is not indicated and a non-invasive method to assess ICP would be desirable (31). Many attempts have been made to find a convenient, non-invasive “estimator” for ICP (32-35). Among these, ONSD ultrasound and TCD has demonstrated to be repeatable, accurate for intraoperative use (20, 25, 36). In particular, the correlation of ONSD and ICP has been established by several authors (23,31). The subarachnoid space surrounding the retrobulbar portion of the optic nerve is distensible and can accordingly expand when cerebrospinal pressure increases. Various TCD-derived formulae have been proposed for the estimation of ICP (35), but it is still not clear which
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one works best. In an animal model (23) where an acute intracranial hypertension was induced, the ICPFVd methodperformed better than other formulae. Bellner et al. (37) found a strong correlation between ICPPI and invasive ICP, but Cardim et al. (38), comparing 4 different TCD derived formulae with invasive ICP in 46 patients with TBI, found that ICPPI was the weakest estimator.
The interactions between the intracranial and the respiratory systems during mechanical ventilation and PEEP application have been studied by several authors, showing conflicting results (39-44). Continuous positive airway pressure has shown to decrease CPP and CBF in head injured patients (41). However, Pulitanò et al. (42) in a recent study demonstrated that PEEP application (from zero to PEEP=8) in pediatric patients undergoing major neurosurgical interventions for tumors removal does not increase ICP, suggesting that PEEP application may be safe, provided that ABPm is maintained. Finally, Mascia and collaborators suggested that ICP significantly increases when PEEP is applied, only in patients where PEEP induces alveolar hyperinflation (“non-recruiters”) with a consequent increase in PaCO2 and ICP, whereas ICP remains constant in patients where PEEP causes alveolar recruitment (“recruiters”) and unchanged PCO2 (45).
Effects of prone positioning and PEEP on nICP estimators
In our study, the mean ONSD, ICPFVd, PI and ICPPI increased significantly after prone positioning and after PEEP application in the prone position (time-points T0-T1, and T0-T2, table 5.2). Isolated PEEP in the prone position did not change ONSD and ICPFVd (time-points T1-T2), but increased ICPPI. All the nICP methods seem to have concordance in the detection of ICP changes (table 5.2). The two-way ANOVA showed that all the nICP methods are strongly influenced by prone positioning but not by PEEP, indicating that real ICP is likely to increase with prone positioning.
Among the methods we assessed, ONSD was dependent just on the different time-points rather than being influenced by other respiratory or hemodynamic variables (table 5.3). Moreover, sonographic ONSD seemed to have the highest sensitivity and specificity for the discrimination between the supine and prone body position (figure 5.1). An optimal cut
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off for discriminating between prone and supine positions was 0.43 cm (figure 5.2). As expected, ICPFVd is the method that is most influenced by hemodynamic variables (in particular by ABPm) and showed a good concordance with ONSD and an acceptable sensitivity and specificity for distinguishing between prone and supine body position (figure 5.1). As expected, ICPPI was strongly influenced by TCD-derived FV, as previously described (19). The observation that ICPPI increased with PEEP application could indicate that it is the only nICP method that can be sensitive enough to detect suspected ICP changes in the setting of increased PEEP or alternatively it could reflect the fact that other factors (apart from ICP) may influence PI during PEEP, in particular ETCO2 (46) (table 5.2, 5.3). In this case, ETCO2 had no significant changes at any studied time-points; we believe that ICPPI resulted to be so sensitive because it is mathematically dependent just from FV values, which significantlychanged after PEEP application.
Influence of respiratory and hemodynamic parameters on nICP
Our findings suggest that even in patients with no head injury, ICP may increase in the prone position. However, intracranial hypertension (ICP > 20 mm Hg as indicated by an ONSD above 0.58 cm (19)) rarely occurred in this cohort. Importantly, the increased estimated ICP detected with non-invasive methods in our case series was not related to an increase of ETCO2 (ranging from 33.6±0.4 to 33.1±0.47 after prone positioning and to 32.5±0.4 after PEEP application, with no significant changes at any studied time-points). Moreover, our multivariate regression analysis confirmed that ETCO2 changes did not influence any of the nICP methods.
ABPm was lower in the supine position with PEEP application (T3) compared to baseline (T0), prone positioning with zero PEEP (T1) and prone positioning with PEEP application (T2). This was probably related to the change of position. However, ABPm as well as nCPP did not increase after prone positioning and PEEP application (T0-T1; T0-T2), suggesting that the increase of ICP registered by non-invasive methods is not the consequence of reduced ABPm, as suggested in a previous study (10).
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Limitations
There are several limitations in this study. The estimation of nICP using both TCD ICPPI and ICPFvd were in fact calibrated using traumatic brain injury patients (25,26). Therefore, absolute values of nICP in patients without any prior intracranial pathology may be artificially elevated. However, in our study we investigated differences in ICP in different body posture and PEEP conditions, rather than absolute values. Calibration error does not affect these differences.
Moreover, to estimate accurately the effects of PEEP and prone positioning on cardiac and cerebral hemodynamics, a more aggressive monitoring should be considered, which should include the invasive measurement of ABPm, the measure of cardiac output, CVP to degree of venous drainage impairment. Moreover, even if in patients with normal respiratory function it is accepted that a constant and predictable gradient between partial pressure of carbon dioxide (PaCO2) and ETCO2 levels exists (47, 48), arterial blood samples with PCO2 determination would be desiderable. These monitoring techniques were not performed in our study as such invasive procedures are rarely indicated in elective neurosurgical procedures.
Furthermore, the data set would have been made more generally complete with the inclusion of an additional data collection time point, in supine positioning at the end of the procedure in the absence of PEEP.
Finally, this study should be considered a pilot study and further studies with larger sample sizes and with different observers repeating the same measurements are warranted. However, despite the limited number of patients included we found high values of partial
η2 and observed power for all the parameters (except ETCO2) (table 5.2), suggesting that
the number of patients was adequate for this study. Spinal surgery cases with prone positioning in patients with intracranial pathology where an invasive ICP monitoring device is already present, should be used to assess the role of noninvasive methods in this group of patients and to compare them with a golden standard.
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CONCLUSIONS
Our findings suggest that in patients without head injury, ICP may increase in prone position, whilst the effect due to PEEP of 8 cmH2O is negligible. TCD-derived formulae and ONSD ultrasound measurement can be both useful, safe, quick and easy techniques to non-invasively detect ICP, but ONSD seems to have the best performance in the detection of changes of body position. The increase in ICP that we detected was rarely estimated to be above 20 mmHg.
Patients at risk to develop intracranial hypertension undergoing spine surgery should be counseled to the risks prone positioning may pose with regard to intracranial hypertension. In these patients, non-invasive ICP monitoring through ONSD ultrasound or TCD could be a valid option.
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Chapter 6 . Effects of Pneumoperitoneum and Trendelenburg
position on intracranial pressure assessed using different non-invasive methods
Chiara Robba, Danilo Cardim, Joseph Donnelly, Alessandro Bertuccio,
Susanna Bacigaluppi, Nicola Bragazzi, Brenno Cabella, Xiuyun Liu, Basil
Matta, Marco Lattuada, and Marek Czosnyka.
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ABSTRACT
Introduction: The laparoscopic approach is becoming increasingly frequent for many different surgical procedures. However, the combination of pneumoperitoneum and Trendelenburg positioning associated with this approach may increase patient’s risk for elevated intracranial pressure (ICP). Because the gold standard for the measurement of ICP is invasive, little is known about the effect of these common procedures on intracranial pressure.
Methods: We prospectively studied 40 patients without any history of cerebral disease, undergoing laparoscopic procedures. Three different methods were used for non-invasively estimating ICP: ultrasonography of the optic nerve sheath diameter (ONSD); Transcranial Doppler-based (TCD) pulsatility index (ICPPI) and a method based on the diastolic component of the TCD cerebral blood flow velocity (ICPFVd). ONSD and TCD were performed immediately after induction of general anaesthesia, after pneumoperitoneum insufflation, after Trendelenburg position and again at the end of the procedure.
Results: ONSD, ICPFVd and ICPPI significantly increased after the combination of pneumoperitoneum insufflation and Trendelenburg position. ICPFVd showed an area under curve (AUC) of 0.80 [95% CI of 0.70-0.90] to distinguish the stage associated with the application of pneumoperitoneum and Trendelenburg position; ONSD and ICPPI showed an AUC of 0.75 [95% CI of 0.65-0.86] and 0.70 [95% CI of 0.58 to 0.81], respectively. Conclusions: The concomitance of pneumoperitoneum and Trendelenburg position can increase intracranial pressure as estimated with non-invasive methods. In high-risk patients undergoing laparoscopic procedures, non-invasive ICP monitoring through a combination of ONSD ultrasonography and TCD-derived ICPFVd could be a valid option to assess the risk of increased intracranial pressure.
