Intra-abdominal hypertension has a high prevalence among critically ill patients and is known to be an independent predictor of mortality (1–3). As the causes for raised intra-abdominal pressure (IAP) are diverse and the association between risk factors and presence of intra-abdominal hypertension is variable, it seems reasonable to screen ICU patients with risk factors for elevated IAP (1, 2).
Ultrasound is routinely used and recommended in critically ill patients with abdominal problems (4–6). It has previously been demonstrated that ultrasound can also be used for noninvasive pressure estimation, for instance, in central veins (7–9), in arteries [(10)], and in the brain [(11, 12)
Ultrasound-guided tonometry is a noninvasive pressure measurement technique. An opaque chamber, filled with an ultrasound-translucent mixture of fluids, is attached to a linear ultrasound probe. This chamber is connected to a manometer and the applied pressure on the chamber is continuously displayed on a monitor.
By applying constant external pressure to the skin, the vertical diameter of this chamber is expected to decrease once IAP rises.
The objective of this proof-of-concept study was to determine the accuracy and reliability of this technique to measure IAP compared with the gold standard. We hypothesized that the vertical diameter of the ultrasound chamber is inversely correlated with the IAP measured by an intravesical catheter. As IAP is, in part, transmitted to the thoracic space, we also investigated whether changes in end-inspiratory airway pressure reflect the respective changes in IAP.
MATERIALS AND METHODS
The study compiled with the Swiss national guidelines for the Care and Use of Laboratory Animals, National Academy of Sciences, 1996, and was performed with the approval of the Commission of Animal Experimentation of Canton Bern, Switzerland (approval number BE 16/14).
The study group consisted of eight domestic pigs. Pigs were chosen because of their size that allowed instrumentation similar to that in use for humans. Considerations for sample size can be found in the statistics section. Three days before the experiment the animals were admitted to the local animal hospital where they were examined by a veterinarian. Before the experiment they were fasted overnight but had free access to water.
In compliance with the three R principle, the same group of pigs were subject to three different, unrelated studies, all involving ultrasound. First, a study investigating intracompartimental pressure in both lower legs was conducted. After a stabilization phase and establishment of a second baseline, the present study on abdominal pressure was conducted. Finally, a study on brain perfusion during increased intracranial pressure was performed. The results from the two studies involving leg compartment and increasing intracranial pressure will be reported separately.
Anesthesia, surgery, and monitoring
The animals (weight 39.5 kg, range 39–42 kg) were premedicated with 20 mg/kg ketamine and 2 mg/kg xylazine intramuscularly, followed by the cannulation of an ear vein. After administration of 0.5 mg/kg midazolam and 0.02 mg/kg atropine, the pigs were orally intubated. They were ventilated using a volume-controlled mode (Servo-I, Maquet Critical Care, Solna, Sweden) with tidal volumes of 8 mL/kg, a positive end-expiratory pressure of 5 mmHg, and a FiO2 of 30%, aiming for a paO2 above 90 mmHg. The respiratory rate was adjusted to maintain arterial pH between 7.35 and 7.45.
After intubation, the animals received 1.5 g of cefuroxime as an antibiotic prophylaxis before surgery. The anesthesia was maintained using propofol (4–8 mg/kg/h) and fentanyl (5–10 mcg/kg/h), and the depth was controlled by repeatedly testing the response to nose pinch. Additional injections of fentanyl (50 μg) were given as needed. Muscle relaxation was maintained with rocuronium infusion during the study measurements (0.5 mg/kg/h) to ensure absence of abdominal muscle contractions as recommended by practice guidelines (13–15).
Intravascular catheters were surgically placed in the left internal carotid artery for invasive blood pressure measurement and in the left internal jugular vein for central venous access.
After midline laparotomy, a Foley urinary catheter was placed surgically into the bladder. Ultrasonic transit time flow-probes (Transonic Systems Inc., Ithaca, NY) of compatible size were placed around the portal vein, the common hepatic artery, and the right renal artery, respectively. An 8.5 French introducer sheath was placed transcutaneously with the tip next to the hepatoduodenal ligament for intraperitoneal pressure measurement. A 20 French chest tube was placed transcutaneously into the peritoneal cavity for subsequent instillation of warmed fluids to increase pressure. Finally, the abdominal wall was closed tightly with running suture so that the intraperitoneal cavity was sealed.
Hemodynamic and respiratory monitoring
Electrocardiogram (ECG) and oxygen saturation (pulse oximetry, attached to the tail) were continuously monitored. Arterial pressure (MAP) and central venous pressure (CVP) were recorded with pressure transducers (xtrans; Codan Medical, Germany) which were calibrated using a water scale and zeroed at atrium level before the measurements. All pressure tracings were continuously displayed on a multimodular monitor (S/5 Critical Care Monitor; Datex-Ohmeda, GE Healthcare, Helsinki, Finland) and subsequently displayed and recorded as 2-min median values in a clinical information system (Centricity Critical Care, GE Healthcare).
Tidal volume, respiratory rate, PEEP, end-inspiratory plateau pressure, and inspired oxygen concentration were continuously monitored and recorded in the same clinical information system.
Intraabdominal pressure monitoring
The intravesical pressure was continuously monitored by connecting the intravesical catheter to an IAP device (UnoMeter Abdo Pressure, unomedical, Denmark). As recommended by the manufacturer, 20 mL of normal saline was injected into the bladder retrogradly and the pubic bone served as reference level.
The intraperitoneal pressure was continuously recorded with a pressure transducer (xtrans; Codan Medical) which was calibrated using a water scale and zeroed at pubic bone before the measurements.
Ultrasonic transit time flowmetry
Blood flow in the portal vein, the hepatic artery, and the right renal artery was continuously measured with ultrasonic transit time flow-probes which were calibrated before insertion as recommended by the manufacturer. Only values with a signal quality >75% were used for further analysis. The measurements were averaged over 1 min.
Ultrasound-guided tonometry “VeinPress”
The VeinPress 2014 system consists of a pressure-transducing chamber filled with ultrasound translucent oil. The front wall of this chamber was applied to the skin surface, the backside attached to a 13–6 MHz linear array ultrasound probe (HFL 38× transducer with a SonoSite M-Turbo Ultrasound Machine, SonoSite Inc, Bothell, Wash) (Fig. 1). The pressure in the chamber was measured and displayed continuously on a monitor after having brought the device in contact to the skin using commercially available ultrasound gel and zero adjustment.
After instrumentation was completed, two investigators performed independently ultrasound-guided tonometry measurement in the middle of the left lower quadrant of the abdominal wall using three different predefined pressure levels (0 mbar, 30 mbar, and 50 mbar). During each pressure application, the vertical diameter of the chamber was measured and the ultrasound loops recorded (Fig. 1). Of note, the displayed size of the organ chamber diameter on the ultrasound screen was approximately 10 times larger than its true size that made it relatively easy to quantify small differences in diameter length. After each examination, the vertical diameter of the chamber in the stored image was re-measured by the respective other investigator, resulting in 4 (online) measurements at each condition. Afterward, IAP (reference: intravesical pressure) was increased to 15 mmHg, and then further in 5 mmHg steps to 40 mmHg by infusing warmed normal saline into the peritoneal cavity. At each IAP level, ultrasound-guided tonometry was repeated. Finally, the IAP was normalized by draining the intraperitoneal fluid through the thoracic drainage tube.
At each IAP level, heart rate, arterial and central venous pressure, inspiratory plateau pressure, flows in the renal artery, the hepatic artery and in the portal vein, as well as the intravesical and the intraperitoneal pressure were recorded. After the experiment, each of the two investigators measured the chamber diameters of their own and of the respective other investigator's images again by using the recorded ultrasound loops, resulting in another four (offline) measurements at each condition. This time, the investigators were blinded to IAP level and applied external pressure level.
Sample size and statistical analysis
No data for sample size calculations were available. We hypothesized a moderate-to-strong correlation (correlation coefficient: 0.8) between the IAP measured intravesically and the respective estimated pressure by ultrasound-guided tonometry. The needed sample size required to detect a significant difference to a correlation coefficient of zero is 8 (with a probability of a type I error (α) of 0.05) and a power (1 − β) of 0.80 (StatsToDo, computer program to calculate sample size requirement for estimating the correlation coefficient).
Despite normal data distribution (Shapiro—Wilk test), values are displayed as median and range for better interpretation of data distribution and discrimination between the different IAP levels. The effect of increasing IAP on the different measurements was assessed using Friedman, followed by Wilcoxon test. For multiple testing (n = 2–3), the statistical significance level was lowered to P < 0.02. Spearman correlation coefficient and regression analysis with curve fitting were used for identifying the relationship between IAP and tonometry assessments and end-inspiratory plateau pressure measurements, respectively. Within and between investigator comparisons of the vertical ultrasound chamber diameter were made using coefficients of variation.
Standard statistical software packages were used for analysis of data (GraphPad Prism 6, GraphPad Software and IBM SPSS Version 21, IBM Corporation). This manuscript adheres to the applicable ARRIVE guidelines.
Systemic hemodynamics and intestinal blood flows
The mean arterial blood pressure increased in all pigs from baseline to the first IAP level and remained stable afterward. The heart rate was not statistically significantly affected by the IAP levels. The flow in the renal artery decreased gradually over the course of the pressure stages and increased after the IAP was normalized. The flow in the portal vein and in the hepatic artery increased from baseline to the first IAP level and decreased gradually thereafter. Both flows increased after the IAP was normalized (Table 1).
Intra-abdominal flows and pressures
The predefined IAP levels were reached in all animals. Intraperitoneal pressures increased in parallel with intravesical pressures but with a large interindividual range at each pressure level (Electronic supplement 1, https://links.lww.com/SHK/A688).
Renal (r = −0.9286, P = 0.0022) and portal (r = −0.8810, P = 0.0072) flows were inversely correlated with IAP levels, whereas hepatic artery flow did not correlate (r = −0.5476, P = 0.1710). The flow in the renal artery decreased linearly with increased IAP. The blood flow in the hepatic artery decreased after an initial rise at pressure level of 15 mmHg. All flows increased after the IAP normalized.
Due to technical difficulties the ultrasound analysis of the first pig could not be evaluated; therefore, the analysis of the ultrasound tonometry consists of a population of seven pigs.
Coefficients of variation for within observer variation were 2.5% (1.1–3.4%; median, range) and between observer 2.5% (0.7%–3.5%). The average of the directly measured online measurements of the two investigators were used for further analysis.
The measured vertical chamber diameter was 14.8 (14.1–15.5) mm without external pressure and decreased with an externally applied pressure of 50 mbar from 14.9 (14.6–15.2) to 12.8 (12.4–13.4) with increasing IAP (P < 0.0001; Electronic supplement 2, https://links.lww.com/SHK/A689). As the values for the externally applied pressure of 30 and 50 mbar were comparable, the 50 mbar-level values were used for further analysis (Electronic supplement 2, https://links.lww.com/SHK/A689). Ultrasound-guided tonometry was able to discriminate between normal and increased values (≥15 mmHg, P = 0.017), between 15 and 25 mmHg (P = 0.018) and between 25 and 40 mmHg (P = 0.017). However, the method could not discriminate (other) nearby IAP levels due to overlapping ranges (Fig. 2).
Correlation of IAP and vertical pressure chamber diameter was highly significant (r = −1, P = 0.0004). However, curve fitting revealed linear in some and quadratic relationship in other animals.
End-inspiratory airway pressure
End-inspiratory airway pressure increased statistically significantly with increasing IAP levels (P < 0.0001; r = 1.0, P < 0.0004). Due to a linear relationship between IAP and end-inspiratory airway pressure in all animals, prediction of IAP by airway pressure was fairly precise (intravesical pressure mmHg = 2.019 × end-inspiratory plateau pressure mmHg−18.46; r2 = 0.9114) (Electronic supplement 1, https://links.lww.com/SHK/A688).
In this proof of concept study values obtained by tonometry-guided ultrasound correlated well with increasing IAP. The method was able to discriminate between normal, moderately, and markedly increased IAP values. In between, tonometry measurements were overlapping. As the vertical diameter of the tonometry chamber decreased continually with increasing IAP in every pig, the method may also play a role in monitoring the evolution of IAP in individual subjects. Nevertheless, we do not suggest that ultrasound-guided tonometry can replace the established, (semi-)continuous assessment of IAP using urinary bladder pressure. Rather, ultrasound tonometry may be used to decide in what patients’ urinary bladder pressure measurement should be established.
Given the small between and within observer coefficients of variation, the accuracy and reliability of the vertical chamber assessments seem excellent and cannot account for the high variability of measurements at a given IAP level. A potential explanation is the relatively small size of the tonometry chamber with respect to the range of tested IAP. This results in low resolution: with a perfectly linear relationship, each 1 mmHg change in intraperitoneal pressure would have resulted in only ½ mm change in the vertical chamber diameter. In addition, it is conceivable that an altered shape of the chamber and a different amount and composition of fluid inside the chamber may improve precision. However, also differences in the compliance of the abdominal wall and in the amount of fluid in the peritoneal cavity at a specific pressure level may have influenced the results (16). These circumstances and different hydrostatic forces in upper abdomen and pelvis may also explain the variable differences between intraperitoneal and intravesical pressures among the animals. These differences are in agreement with published data in different animal models of increased IAP (16–18).
The nature of an animal study, the relatively small sample size, and the infusion of muscle relaxants during the measurements may limit the transferability of the results to clinical practice. Nevertheless, studies in humans demonstrate that deep muscle relaxation in comparison with moderate or no muscle relaxation may decreases IAP but not its variability (19–21). The strengths of the method are its noninvasiveness, easy applicability, and the high reproducibility of the results.
Given the widespread use and availability of ultrasound in anesthesia, emergency departments, and in the ICU both for diagnostic and therapeutic purposes, we think that ultrasound-guided tonometry has the potential as a screening tool in the acute care setting in patients with risk factors for developing increased IAP or abdominal compartment syndrome.
Increasing IAP is transmitted to the intrathoracic space and therefore affects lung mechanics. By increasing pleural pressure both total lung capacity and lung compliance decrease. This is reflected by changes in the plateau pressure at a given tidal volume (22, 23). In our model, the rise in IAP was closely tracked by respective changes in plateau pressure. This finding highlights the clinical importance of lung mechanics also in circumstances of elevated IAP and may help to detect and understand the effects of intra-abdominal hypertension on cardiopulmonary function as well as in guiding ventilator strategies.
The initial increase in blood pressure may present a reaction of the animals to the fluid infusion. The observed changes in portal and renal blood flow were inversely correlated with IAP levels. However, blood flow in the hepatic artery was preserved. These findings are in accordance with the literature and underline the importance of hepatic arterial supply for liver perfusion (24–26).
In conclusion, in our model increased IAP can be detected reliably by ultrasound-guided tonometry. Nevertheless, the method will need further development and evaluation in clinical studies.
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