Comparison of Different Tidal Volumes for Ventilation in Patients with an Acute Traumatic Cervical Spine Injury
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.360926
Source of Support: None, Conflict of Interest: None
Keywords: Cervical spine injury, high tidal volume, low tidal volume, ventilation, ventilator-free breathing, weaning
Cervical spinal cord injury (CSCI) imposes a huge health care burden worldwide. It entails a myriad of complications, and ventilator dependence is one of the most critical. High tidal volume (HTV) ventilation for weaning following CSCI is described to recruit distal airways, stimulate surfactant production, and improve oxygenation. In acute CSCI, there is flaccid muscle tone and increased abdominal compliance, and peak pressure (PPeak) rarely exceeds 30 cmH2O, which decreases the chances of barotrauma. The literature points toward the advantages of HTV (>20 mL/kg) ventilation in SCI.,, However, with the introduction of acute respiratory distress syndrome (ARDS) net guidelines, there is an ever-increasing trend advocating low tidal volume (LTV) ventilation (6–8 mL/kg) due to its lung-protective effects. The disadvantages of LTV ventilation include the requirement of heavy sedation, increased atelectasis, and patient–ventilator asynchrony among others. Moreover, its efficacy on weaning in patients with acute CSCI has not been described.
Thus, we planned this randomized controlled trial to see the effect of two different tidal volumes; Group H (12–15 mL/kg) and group L (6–8 mL/kg) on days to achieve ventilator-free breathing in acute CSCI. Secondary objectives were to see the PaO2/FIO2 (partial pressure of oxygen: the fraction of inspired oxygen) ratio, the incidence of barotrauma, atelectasis, ventilator-associated pneumonia (VAP), ARDS, requirement of vasopressor drugs, total duration of hospital stay, and mortality in each group.
Following the approval from the Institute Ethics Committee (IECPG/349/7/2018) and registration in Clinical Trial Registry India (CTRI) (CTRI/2018/10/016028), informed consent was obtained from the patient/nearest kin. This prospective randomized controlled parallel-group, single-blinded study was conducted on patients between 18 and 65 years of age with acute traumatic CSCI admitted within 24 h of injury to the neurotrauma intensive care unit (NICU) from September 2018 to April 2019.
All patients admitted to NICU received standard treatment as per the hospital protocol and in accordance with advanced trauma life support guidelines. The level and severity of SCI were determined at the time of admission according to the 2019 revision of the international standards for neurological classification of spinal cord injury (ISNCSCI). Patients with an associated head or chest injury, history of aspiration, chronic cardiopulmonary disease, obstructive sleep apnea, and body mass index ≥30 kg/m2 were excluded. Patients were randomized into two groups using a computer-generated block randomization chart with four patients per block [Figure 1]. Opaque sealed envelopes were used for group allocation. Group H was ventilated with 12–15 mL/kg (IBW) tidal volume and group L received 6–8 mL/kg (IBW) tidal volume.
Ideal body weight (IBW) was calculated using Broca's index. Height was estimated using arm span. Ideal body weight was utilized to calculate the ventilator tidal volume. Ventilation was initiated on an assist mode for a period of 6 h using a decelerating ramp flow pattern and a tidal volume between 9–10 mL/kg, respiratory rate 10–12 breaths/min, titrated to arterial carbon dioxide levels between 35 and 40 mmHg. The lowest possible FIO2 was selected that achieved SPO2 of ≥95%. The respiratory rate was adjusted to keep the arterial blood gas (ABG) pH between 7.30 and 7.45 at all times. ABG was done at least twice at 8 am and 4 pm daily as per the ICU protocol. If the desired pH was not achieved, then ABGs were repeated as needed until it was achieved. Baseline parameters were noted that included tidal volume, peak pressure, mean arterial pressure (MAP), peripheral capillary oxygen saturation (SPO2), heart rate (HR), and PaO2/FIO2 ratio.
Tidal volume was gradually increased by 1 mL/kg every 2 h in Group H with continuous monitoring of peak pressures. At any point in time, if the peak pressures exceeded 40 cm H2O, no further increase in tidal volumes was made and the tidal volume achieved in mL/kg was noted. If the peak pressures remained <40 cm H2O, then the tidal volumes were increased to ≥12 mL/kg (IBW) with a maximum set at ≤15 mL/kg (IBW). Positive end-expiratory pressure (PEEP) was set at 5 cm H2O for both groups. Tidal volume was gradually decreased by 1 mL/kg every 2 h in group L with monitoring for respiratory acidosis, until the tidal volume achieved was ≤8 mL/kg (IBW) with a respiratory rate (RR) ≤30 cycles per min and pH ≥7.30. Acidosis was monitored and the ABG analysis was done as per the protocol mentioned above. Further decreases in tidal volume were made if there were no respiratory acidosis with a minimum set at 6 mL/Kg (IBW).
Intravenous midazolam 0.03–0.2 mg/kg/h and fentanyl 20–50 μg/h was titrated to the Richmond Agitation Sedation Scale (RASS) with a target score of zero. A daily sedation-free period of 2 h was given for neurological assessment. Routine care of patients included salbutamol nebulization, chest physiotherapy, cough assist device, abdominal binder, venous thromboembolism prophylaxis, and incentive spirometry. Patients were observed until they were discharged from the hospital after VFB was achieved or in-hospital mortality, whichever was earlier. The number of days to achieve VFB was measured from the day of onset of mechanical ventilation in the NICU.
Daily tidal volume, Ppeak, HR, MAP, PaO2:FIO2ratio, SPO2, PaCO2, base excess, and RASS scores were recorded. Each parameter was noted three times daily and the average of the three values was obtained for each day the patient was dependent on a ventilator. The mean of the average values for each day was then taken for the final analysis. The requirement of vasopressor drugs, tracheostomy, and incidence of barotrauma, atelectasis, VAP, and ARDS was noted.
ARDS was defined by Berlin's criteria. If the patient in group H developed ARDS, the ventilation strategy was changed to lung-protective ventilation as per the ARDS net guidelines and the patient was provided LTV ventilation (group L). Atelectasis was defined based on chest X-rays. VAP was Defined as per the Centre for Control of Communicable Diseases criteria. Pulmonary barotrauma included complications such as pneumothorax, pneumomediastinum, and subcutaneous emphysema.
Pressure support ventilation (PSV) or progressive ventilator-free breathing (PVFB) on T-piece was used for weaning., Weaning was commenced when the patient met the following criteria: vital capacity: >10 mL/Kg (IBW), respiratory rate: 10–12 breaths/minute, minute ventilation: <10 L/min, PaO2 >80 mmHg with FIO2 at ≤0.4, PaCO2 <45 mmHg, rapid shallow breathing index (RSBI) <105, clear or improving chest radiographs, stable vital signs and no complications such as fever, sepsis, hemodynamic disturbance, ABG abnormalities, and altered mentation. VFB was considered to be achieved when the patient comfortably tolerated 24 h without the requirement of mechanical ventilation.
The sample size was calculated based on the study done by Peterson et al. To detect a difference of 21 days between HTV and LTV with 80% power at a 5% level of significance with a two-sided test, we studied 28 patients in each group. IBM Statistical Package for Social Sciences (SPSS) version 21 for Windows® was used for data analysis. Descriptive statistics were used to present epidemiological data. Continuous normally distributed variables (age, BMI, HR, MAP) were expressed as the mean and standard deviation, and skewed data (VFB achieved, atelectasis onset, vasopressor support duration, and Hospital stay) were expressed as median and interquartile ranges (IQR). Categorical variables were expressed as n (%). The student's t-test was used to compare continuous data and Mann-Whitney U-test was used for skewed data. Categorical variables were compared using the Chi-square test or Fisher's exact tests. A P value of ≤0.05 was considered statistically significant. The Kaplan Meier survival probability was estimated for the two groups through the KM curve, the dependent variable considered was the occurrence of death and time was the total duration of ventilation. Log-rank test was applied to test significance.
A total of 56 patients were randomized. [Figure 1]. Demographic variables and injury severity in each group are shown in [Table 1]. The results are described as an intention to treat analysis. Days to achieve ventilator-free breathing in group H and group L were a median of 3 (2,56) days and 8 (2,50) days, respectively (P = 0.33). [Figure 2]. Days to achieve ventilator-free breathing and other study variables are described in [Table 2]. A total of 23 (82%) patients in group H and 19 (68%) patients in group L achieved VFB on or before 30 days (P = 0.01).
The ventilator parameters, incidence of complications, and patient hemodynamics are described in [Table 2]. A total of 4 (14%) patients in group H and 10 (36%) in group L developed ARDS (P = 0.12). The overall mortality was observed in 14 patients out of 56 patients, 5 (18%) patients in group H and 10 (36%) in group L. Mortality was high in AIS-A patients with 10 deaths (5 in group H and 5 in group L), one patient died each in AIS B, C and D. The level of injury was C1-C4 in 3 patients and C5-6 in 11 patients who died. The cause of death was sepsis in 13 patients and sudden cardiac arrest in 1 patient. There was no significant difference in survival between the two groups [Figure 3].
There is a trend toward using LTV (6 mL/kg) in critical illness after ARDS network investigators reported significantly lower mortality and higher VFB associated with its use., The applicability of these findings in patients with acute SCI is variable. HTV 20 mL/kg has been reported to facilitate earlier weaning in CSCI in rehabilitation centers.,,, Most of the existing literature on this topic is retrospective, and only a few prospective studies have addressed this issue in patients with acute CSCI injury., A study in sub-acute traumatic tetraplegics using high (20 mL/kg) versus standard tidal volumes (10 mL/kg) by Fenton et al. saw no difference in median days to wean (median 14.5 days and 14 days). However, Hatton et al. in their retrospective cohort study in patients with acute CSCI reported that HTV was associated with higher ventilator dependence (82% vs. 38%, P < 0.001) which was attributed to a higher level and completeness (AIS-A & AIS-B) of injury, older age, and earlier year of care This prospective study in patients with acute CSCI and evaluated the utility of LTV (6–8 mL/kg) and HTV (12–15 mL/kg) ventilation and found them comparable in time to achieve VFB. We used tidal volumes far lesser than 20 mL/kg and saw its effect on weaning and vital parameters. Our results are similar to those observed by Fenton et al in sub-acute traumatic tetraplegics. However, the patients we studied were of acute CSCI (within 24 h of admission). We looked into the feasibility and advantages of either type of ventilation strategy on respiratory physiology, hospital stay, and mortality. Though LTV has been known to offer advantages in patients with ARDS, no distinct advantage of the strategy was seen in patients with acute CSCI.
We found a relatively higher PaO2:FIO2 in group H than the group L. A PaO2:FIO2 ratio of <300 on day 3 (P = 0.03) has been reported as a predictor of prolonged mechanical ventilation (>7 days). We could not find any advantage of higher PaO2:FIO2 in terms of time to wean in group H. HTV, 15–20 mL/kg has been advocated for the prevention and early resolution of atelectasis in SCI.,,,, HTV is said to increase surfactant production, promote the recruitment, and prevent airway collapse and complications such as barotrauma and altered hemodynamics are less in SCI, especially tetraplegics due to the flaccidity of abdominal muscles and increased compliance.,,, No barotrauma was reported in our study.
Studies done on tetraplegics found that the incidence of pneumonia post-admission was similar with both low and HTV., However, a study done on acute CSCI reported an increased incidence of VAP in patients ventilated with HTV as compared to standard ventilation (68% vs. 44%, P = 0.06). Factors associated with an increased incidence of VAP included a higher level of injury, complete injury, older age, male gender, delayed intubation, and the presence of chest trauma., We found a higher incidence of VAP in patients being ventilated with LTV (32%) as compared to patients being ventilated with HTV (11%), (P = 0.05). The reason could not be exactly defined but may be due to lesser atelectasis associated with higher tidal volumes. The reported incidence of ARDS is similar in high HTV and LTV ventilation (1 vs. 0, P = 0.36) and is similar to our study, (14% vs. 36%, P = 0.12).
In a cohort study in acute CSCI patients, higher tracheostomy rates were reported in the HTV group as compared to the standard tidal volume (86% vs. 63%, P = 0.05). In the acute phase, the need for tracheostomy is dependent upon the ability to achieve weaning and development of pulmonary complications besides the level and severity of the injury. Because all these variables were comparable in both our groups, so was the rate of tracheostomy.
There is a paucity in the literature on the effect of high and LTV ventilation on the requirement of vasopressors in acute CSCI patients. The reported incidence of vasopressor requirement is up to 67% in patients with cervical spinal cord injury in a study from the same institute.
Our study showed comparable vasopressor requirements in both groups. The mean arterial pressures were also comparable in both groups.
Patients with SCI have prolonged hospitalization.,, Prolonged mechanical ventilation, type of injury, and use of vasopressors have been reported as predictors of mortality in the literature., Mortality was high in AIS-A patients with 10 deaths out of 14 deaths. The level of injury was C1-C4 in 3 patients and C5-6 in 11 patients. Our data point toward the severity of injury to be a more important predictor of mortality as compared to the level in patients with cervical spinal cord injury.
We did not use tidal volume up to 20 mL/kg; rather, our study looked into the utility of two common ventilation strategies to achieve VFB in patients with acute spinal cord injury. Though we did not find any statistical difference in the achievement of VFB in either group, incidence of atelectasis, barotrauma, or vasopressor requirement with the use of either ventilation strategy, the findings were clinically relevant. Notable clinically beneficial effects of HTV were low incidence of VAP and atelectasis, whereas the difference in the incidence of ARDS and in-hospital mortality was better explained by the severity of injury in these subsets of patients. Better oxygenation was achieved with the use of higher tidal volumes but then it did not translate to any other advantage. Though our study highlights the utility of two ventilation strategies in real-life scenarios, it has its limitations. We included patients with variable AIS scores. We matched the severity scores (AIS A, B and AIS C, D) between the two groups, but due to the small sample size, sub-categorizing the level of injury (C1-6) and AIS (A-D) was not possible. Patients were not followed after achieving VFB and therefore, re-intubation data and subsequent ventilator dependence are not known. Multicentric prospective studies with higher sample sizes are warranted to further establish the above findings.
Our study found that both high (12–15 mL/kg) and LTV (6–8 mL/kg) ventilation can be used for Ventilation in acute CSCI to achieve VFB. However, oxygenation (PaO2:FIO2) was significantly higher with HTV. The incidence of pulmonary complications, such as VAP and ARDS, length of hospital stay, and vasopressor support, were similar in both groups. Further prospective multicenter studies with larger sample sizes and longer follow-ups are warranted to assess the advantage of one modality over the other.
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Conflicts of interest
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[Table 1], [Table 2]