Dynamic parameters of fluid responsiveness in the operating room

Background Reliable assessment of fluid responsiveness with pulse pressure variation (PPV) depends on certain ventilation-related preconditions; however, some of these requirements are in contrast with recommendations for protective ventilation. Objective The aim of this study was to evaluate the applicability of PPV in patients undergoing non-cardiac surgery by retrospectively analyzing intraoperative ventilation data. Material and methods Intraoperative ventilation data from three large medical centers in Germany and Switzerland from January to December 2018 were extracted from electronic patient records and pseudonymized; 10,334 complete data sets were analyzed with respect to the ventilation parameters set as well as demographic and medical data. Results In 6.3% of the 3398 included anesthesia records, patients were ventilated with mean tidal volumes (mTV) > 8 ml/kg predicted body weight (PBW). These would qualify for PPV-based hemodynamic assessment, but the majority were ventilated with lower mTVs. In patients who underwent abdominal surgery (75.5% of analyzed cases), mTVs > 8 ml/kg PBW were used in 5.5% of cases, which did not differ between laparoscopic (44.9%) and open (55.1%) approaches. Other obstacles to the use of PPV, such as elevated positive end-expiratory pressure (PEEP) or increased respiratory rate, were also identified. Of all the cases 6.0% were ventilated with a mTV of > 8 ml/kg PBW and a PEEP of 5–10 cmH2O and 0.3% were ventilated with a mTV > 8 ml/kg PBW and a PEEP of > 10 cmH2O. Conclusion The data suggest that only few patients meet the currently defined TV (of > 8 ml/kg PBW) for assessment of fluid responsiveness using PPV during surgery.


Introduction and background
The use of pulse pressure variation (PPV) is commonly recommended to predict intraoperative fluid responsiveness [8,16].To reliably assess fluid responsiveness by this parameter using accepted thresholds, the presence of sinus rhythm during controlled mechanical ventilation with a tidal volume (TV) of > 8 ml/kg predicted body weight (PBW) is essential [12,14,15,21,27].Other more debated requirements include a low positive end-expiratory pressure (PEEP) ≤ 5 cmH2O [11,21], closed chest [26] and normal intra-abdominal pressure [6,18], which conflicts with the capnoperitoneum in minimally invasive laparoscopic surgery.
The application of TV of > 8 ml/kg PBW challenges daily clinical practice because it conflicts with the standards of a lung protective ventilation strategy.Adopted from ventilation in acute respiratory distress syndrome (ARDS), low TVs (6-8 ml/kg PBW) proved to be beneficial in other populations and have become the preferred intraoperative approach [9,20].Common thresholds for dynamic preload parameters, such as PPV, have been investigated for higher TVs, raising the question of their applicability under current ventilation strategies [12,15].
This study aimed to evaluate intraoperative ventilation parameters with respect to the feasibility of using PPV to guide fluid therapy in three large tertiary care centers in Germany and Switzerland.The primary endpointof this studywas to determinethe number of patients undergoing surgery who met mTV/kg PBW criteria at certain averaged data.The PBW was calculated using the Devine formula: for men PBW = 50 kg + 0.91 ×(height (cm) -152.4 cm) and for women PBW = 45.5 kg + 0.91 × (height (cm) -152.4 cm).Subsequently, the mean PEEP was classified into three groups (< 5 cmH2O; 5-10 cmH2O; > 10 cmH2O) and mTV was grouped into mTV < 6 ml/kg PBW, mTV = 6-8 ml/kg PBW, and mTV > 8 ml/kg PBW.
In addition to demographic parameters, medical and surgical data, including diagnosis, name and duration of the procedure, and American Society of Anesthesiologists (ASA) physical status were analyzed.
Surgery was divided into categories by specialty.Abdominal procedures included urological, gynecological, and general surgical procedures.A distinction was made between laparoscopic and non-laparoscopic procedures.The second category included trauma/orthopedic as well as neurosurgery cases and the third category included thoracic cases.

Statistical analysis
All hospitals used a customized version of COPRA (COPRA System GmbH, Berlin, Germany) as PDMS and data were extracted into Excel sheets (Microsoft Excel, Microsoft Corporation, Redmond, WA, USA).Statistical Product and Services Solutions (SPSS) software (IBM SPSS Inc, Armonk, NY, USA) was used for statistical analysis.Demographic and medical data were expressed as means ± SD together with the range.Where applicable, frequency is stated.

Results
A total of 63,685 anesthesia records were received from the participating centers.After applying the exclusion criteria described above, 3398 records remained for further analysis (see .Fig. 1), with 7.1% of the data evaluated from the Hirslanden Hospital Network, 63.3% from Charité Universitätsmedizin Berlin and 29.4% from the University Medical Centre Rostock.Minimum requirements for ventilation, demographic and medical data were set for inclusion in the analysis.Only records that met all the specified inclusion and exclusion criteria were included.PEEP positive end-expiratory pressure, etCO2 end-tidal partial pressure of carbon dioxide   Excluding procedures lasting less than 120 min, the mean operating time was 228.5min (± 109.6min).Abdominal procedures accounted for 75.5% of the data analyzed, composed of 33.9% using a laparoscopic approach and 41.6% a non-laparoscopic approach.Further, 18.6% were assigned to trauma/orthopedic surgery and neurosurgery and 2.6% procedures to thoracic surgery.Of the interventions, 3.3% could not be clearly categorized to a specialty or approach.
Heart rhythm was documented in 25% (n = 850) of the evaluated data and classified as sinus rhythm in 93%.
Ventilation data for the overall collective are shown in .In 97.4% of all included cases, a mean PEEP in the range of 5-10 cmH2O was applied, while in 2.6%, mean PEEP greater than 10 cmH2O was used.Of the higher mean PEEP levels of > 10 cmH2O, 88.6% were recorded during abdominal surgery with equal distribution between laparoscopic and non-laparoscopic approaches.During thoracic surgery, only mean PEEP values between 5-10 cmH2O were set.The mean respiratory rate recorded was 12.8 (± 1.7) breaths/min, with a maximum of 26.1 breaths/min.
Of all included cases 75% were ventilated with a mTV of 6-8 ml/kg PBW, while a mVT greater than 8 ml/kg PBW was applied in 6.3%.Lower mTVs of less than 6 ml/kg PBW were used in 18.6%.In abdominal surgery, 5.5% were ventilated with mTVs greater than 8 ml/kg PBW, which did not differ between laparoscopic and non-laparoscopic approaches (contributing 44.9% and 55.1%, respectively to abdominal surgery).None of the recorded cases of thoracic surgery were ventilated with a mTV greater than 8 ml/kg PBW.
The data show that 6.0% of all cases included in the study were ventilated with a mTV of > 8 ml/kg PBW and a PEEP of 5-10 cmH2O, while 0.3% were ventilated with a mTV > 8 ml/kg PBW and a PEEP of > 10 cmH2O.

Discussion
Dynamic preload parameters, such as PPV, are beneficial for goal-directed fluid management during intraoperative procedures [8].The rationale of this retrospective analysis was to determine whether intraoperative ventilation meets the criteria for using dynamic preload parameters in daily clinical practice.
In the analyzed cases the magnitude of the TV appears to be the main point of contestation.Within the population studied, only a small proportion met the target TV of greater than 8 ml/kg PBW, which continues to be regarded as mandatory for the correct assessment of fluid responsiveness with the accepted cut-off values [12,15], albeit meta-analysis suggesting a "fair performance" of PPV during lower TVs [1].Lower TVs were preferred for intraoperative ventilation.This is most likely due to following a lung protective ventilation strategy [10].Lower TVs prompt less variation in intrathoracic pressure, which may then not be high enough to trigger sufficiently large preload changes to deflect PPV, despite fluid responsiveness above common thresholds [12,15].
The effect of elevated PEEP on PPV has been debated with conflicting results.While some studies reported good predictive quality at PEEP levels > 5 cmH2O [22], other authors argued that cardiac filling and subsequently PPV are affected by higher PEEP levels [11,21]; however, as there is no standardized value for PEEP for the accurate assessment of fluid responsiveness using PPV at its common thresholds, it was necessary to categorize the data into different PEEP groups and analyze different levels of PEEP in a sub-group analysis.In the majority of our cases, a mean PEEP of 5-10 cmH2O was applied, which is recommended to prevent atelectasis [4,10].Raising PEEP reduces venous return, leading to a decrease in left ventricular preload and, thus, higher PPV values.Nevertheless, these high values should be interpreted with care and should not result in uncritical intraoperative fluid therapy, as these changes resolve after extubation.
Furthermore, De Backer et al. found that high respiratory rates limit the informative value of preload parameters [3].In short respiratory cycles, notably at respiratory rates of 30-40/min, preload changes were attenuated, leading to reduced PPV.In this study, the mean respiratory rate was markedly below these respiratory rates, suggesting that respiratory rates did not limit the assessment of fluid responsiveness in an intraoperative setting.
One-lung ventilation (OLV) is a controversially discussed restriction of dynamic preload indicators, as it might affect pressure transfer from the ventilator to intrathoracic vessels [24].In the recording of the data, no distinction was made between one-lung ventilation and ventilation of both lungs.The OLV is a standard anesthesia technique to facilitate thoracic surgery.For these reasons, data of patients undergoing thoracic surgery cannot be analyzed collectively with those of other surgical disciplines; thus, data with possible OLV were evaluated separately.In this group no patient had a mTV greater than 8 ml/kg PBW.This is not astonishing, as the use of low TVs during OLV is recommended to prevent acute lung injury, as these volumes are applied to a single ventilated lung [4, 7, 23].There are data to support the applicability of PPV for pre-dicting fluid responsiveness during OLV [13]; however, it is not common practice.
For one third of all cases analyzed, a laparoscopic approach was chosen for intraabdominal surgery.Pneumoperitoneum during laparoscopic approach increases intra-abdominal pressure, which might affect the applicability of PPV.Therefore, laparoscopic abdominal surgeries were analyzed separately.Studies suggest that this parameter remains indicativewhenthreshold values are increased [5].Research is required to define thresholds for the use of preload parameters under elevated abdominal pressures.
Sinus rhythm is another absolute requirement [17] to use PPV as a guide for intraoperative fluid therapy.Arrhythmia leads to variations in stroke volume and pulse pressure independent of heart-lung interactions.In our routine care anesthesia records, cardiac rhythm was only documented in one quarter of the evaluated cases, as this had to be performed manually by the anesthesiologist.While the vast majority of cases where cardiac rhythm was documented showed sinus rhythm, it is not possible to extrapolate this to the whole study group.
The analyzed data indicate that lung protective ventilation strategies are applied in the majority of patients undergoing surgery.A different approach is a tidal volume challenge, where a transient increase in TV to at least 8 ml/kg PBW for 1min is initiated prior to determining PPV [15,19].In order to evaluate fluid responsiveness by PPV in as large a patient population as possible, current thresholds need to be reconsidered in different intraoperative settings.

Limitations
We gathered a dataset with more than 63,000 anesthesia records, each containing at least 6 variables per 5-min interval.During the first review, we discovered that the parameters were heterogeneous.They were recorded in different units, not only from hospital to hospital, but also within the individual data set, especially for TV (ml or l) and etCO2 (kPa or mmHg).The major issue was that the respective unit was not attached to the value provided by the ventilator.Thus, each dataset had to be analyzed individually.Each value was checked for plausibility and appropriate units were assigned accordingly.Conversion of units was particularly difficult with those values that were outside the normal range of both units, as a distinction had to be made between a particularly low value in one unit and a very high value in the other.Secondly, it was not possible to only collect data from procedures carried out with the patient under general anesthesia with controlled mechanical ventilation as requested.The chart received values from every anesthesia machine that was turned on after the electronic record had been linked to the respective workstation, irrespective of the type of anesthesia (monitored anesthesia care, regional, neuraxial or general anesthesia).
As the primary task was to identify patients with controlled mechanical ventilation as a prerequisite for the accurate use of dynamic variables for fluid responsiveness, a series of filters were applied.As procedures characteristically performed with bag-mask or laryngeal-mask ventilation are seldomly employed in clinical practice for procedures exceeding 2h [2, 25], any procedures lasting less than 120 min were excluded.Furthermore, by excluding all procedures with a duration < 120 min, it should be ensured that the evaluation is based on a sufficient number of valid measurements.Moreover, interventions with an averaged etCO2 of less than 3.44 kPa (80% of the lower standard value of etCO2) were excluded, as etCO2 is not accurately measured during monitored anesthesia care or bag-mask ventilation due to high leakage in the ventilation circuit, often resulting in very low etCO2 values.To account for the abovementioned unit conversion issue, we excluded datasets with etCO2 values that exceeded the upper standard value by more than 20% (equivalent to 6.84 kPa) together with the values that came below the lower standard value by more than 20% (3.44 kPa).
In addition, the intraoperative use of cardiopulmonary bypass, common in cardiac surgery, confounds the averaged ventilation data.Depending on the anesthesiologist, either no ventilation was applied (with the ventilator completely turned off or in manual/spontaneous mode), or the ventilator was set to HLM mode with minimal ventilation during extracorporeal circulation.As both forms decrease the averaged etCO2, minute volume, and respiratory rate, cardiac surgery was excluded.
A considerable number of records were excluded from the analysis due to incomplete datasets.This meticulous selection process aimed to prioritize datasets that met strict criteria for completeness and reliability, while maintaining the overall integrity of the research, taking into account that patients meeting the applicability criteria for PPV might have been excluded.Ventilation data were extracted and averaged by the PDMS.Data validation was required by the attending anesthesiologist prior to data release; however, the inclusion of implausible data in the calculation cannot be excluded.By averaging the values, no statement can be made as to whether the parameters were not temporarily fulfilled at another time during surgery.Furthermore, the data from Charitè-Universitätsmedizin Berlin accounted for more than two thirds of the total data.Despite the absence of any significant discrepancies between the centers, the individual hospitals exhibited different influences on the final analysis.
The predominance of abdominal surgery in the datasets can be attributed to the prevalence of general surgical procedures which are recorded by the PDMS in different hospital settings.Furthermore, the increasing use of regional anesthesia and neuraxial techniques in trauma surgery resulted in the exclusion of considerable trauma surgery data.It is important to note that our study does not reflect accurate frequency of abdominal surgical surgery in clinical practice.

Conclusion
-Our data suggest that only a minority of all patients undergoing anesthesia currently meet recommended tidal volumes for assessing fluid responsiveness by pulse pressure variation (PPV).This implies that ventilation requirements are at odds with current lung protective ventilation strategies.-The use of PPV as a guiding factor for intraoperative fluid therapy requires critical revaluation.Individualized adjustments to ventilation settings, such as a "tidal volume challenge", may be necessary to ensure reliable control of fluid therapy during surgical procedures.

Table 1
Inclusion and exclusion criteria Minimum

Table 3 ;
in .Table 4 they are categorized by surgical specialty.

Table 4
Ventilation data by the surgical field Data are presented in mean ± standard deviation (SD) etCO2 end-tidal partial pressure of carbon dioxide, PEEP positive end-expiratory pressure, PBW predicted body weight