Near-fatal pulmonary embolism: capnographic perspective

DEAR EDITOR,

Massive pulmonary embolism (MPE) is a condition that causes sudden changes to the cardiopulmonary system^1-5 and is associated with high morbidity and mortality. Methods that detect those changes in real time, especially noninvasive ones, can be very useful. They can also indicate whether the MPE is likely to improve or not.

To address the clinical scenario of MPE, one may make use of noninvasive devices with software that monitors respiratory mechanics and volumetric capnography (VCap) data, online and offline, providing information that may indicate ventilation-perfusion mismatch, in MPE or in other diseases.

The respiratory profile monitor (CO₂SMO PLUS DX-8100; Respironics, Murrysville, PA, USA) provides and records variables such as end-tidal partial pressure of CO₂ (PetCO₂), CO₂ output (VCO₂), the phase II slope of the capnogram (SII), the phase III slope of the capnogram (SIII)―also known as the alveolar plateau, respiratory rate (RR), inspiratory tidal volume (V_Ti), expiratory tidal volume (V_Te), inspiratory time, expiratory time, alveolar minute volume (MValv), peak inspiratory flow, and peak expiratory flow.

This was an observational study of pigs induced to MPE through the injection of autologous clots, during spontaneous ventilation (FiO₂ = 0.21). Our aim was to record, observe, and analyze the behavior of respiratory mechanics parameters, especially VCap data.

We evaluated numerical variables (Table 1) and curves (Figures 1A, 1B, and 1C).

Table 1
Respiratory mechanics, gas exchange, and hemodynamic variables.

Variable	Time point
	T0	T1	T2	T3	p
RR (breaths/min)	47 ± 9	48 ± 8	53 ± 11	54 ± 12	0.061
MValv (L)	4.0 ± 0.9	10.6 ± 2.9	9.9 ± 3.8	7.8 ± 1.6	< 0.0001
VDalv (L)	2.4 ± 0.6	4.0 ± 0.8	4.1 ± 1.4	3.8 ± 1.1	< 0.0001
PetCO2 (mmHg)	40.1 ± 2.0	11.0 ± 2.7	16.9 ± 5.5	19.7 ± 4.6	< 0.0001
VCO2 (mL/min)	95 ± 23	83 ± 20	126 ± 25	114 ± 27	0.001
VCO2/VTe (mL/L/min)	0.69 ± 0.10	0.28 ± 0.08	0.49 ± 0.10	0.53 ± 0.10	< 0.0001
VCO2/VTalv (mL/L/min)	1.09 ± 0.16	0.40 ± 0.13	0.70 ± 0.16	0.79 ± 0.15	< 0.0001
SII (mmHg/L)	1414.3 ± 232.5	185.1 ± 66.8	330.7 ± 128.4	441.1 ± 125.0	< 0.0001
SIII (mmHg/L)	56.73 ± 11.86	−1.10 ± 1.16	7.93 ± 10.06	13.02 ± 10.22	< 0.0001
SII/PECO2	107.61 ± 33.42	31.15 ± 8.06	38.86 ± 12.09	51.35 ± 12.92	< 0.0001
SIII/PECO2	4.247 ± 1.188	−0.185 ± 0.210	0.788 ± 0.898	1.366 ± 0.758	< 0.0001
SIII/PetCO2	1.409 ± 0.247	−0.095 ± 0.108	0.378 ± 0.472	0.603 ± 0.362	< 0.0001
SIII/VTe	0.427 ± 0.137	−0.004 ± 0.004	0.031 ± 0.037	0.060 ± 0.043	< 0.0001
Intercept Y2 (mmHg)	−48.7 ± 3.7	−9.5 ± 2.1	−15.0 ± 5.8	−19.2 ± 4.8	< 0.0001
Intercept Y3 (mmHg)	35.8 ± 1.7	11.8 ± 2.1	15.7 ± 4.1	18.2 ± 3.0	< 0.0001
P1V (mL)	28.0 ± 5.1	43.5 ± 5.9	41.5 ± 7.4	38.0 ± 6.0	< 0.0001
P2V (mL)	36.0 ± 5.0	63.0 ± 9.3	59.3 ± 11.4	52.7 ± 8.7	< 0.0001
PFI (L/min)	25.5 ± 3.6	38.7 ± 4.9	38.6 ± 7.7	34.6 ± 3.1	< 0.0001
PFE (L/min)	16.3 ± 3.4	49.2 ± 9.8	39.4 ± 16.2	31.8 ± 9.4	< 0.0001
Ti (s)	0.49 ± 0.06	0.65 ± 0.11	0.57 ± 0.09	0.53 ± 0.12	< 0.0001
Te (s)	0.85 ± 0.20	0.74 ± 0.26	0.66 ± 0.21	0.65 ± 0.20	0.0348
PaCO2 (mmHg)	44.92 ± 4.44	48.22 ± 5.97	45.37 ± 5.82	43.52 ± 6.21	0.158
P(a-et)CO2 (mmHg)	4.8 ± 2.8	37.2 ± 5.8	28.5 ± 4.5	23.8 ± 3.5	< 0.0001
DC (L/min)	4.9 ± 1.0	2.7 ± 1.0	3.6 ± 1.1	3.9 ± 1.3	< 0.003

• T₀: baseline; T₁: endpoint; T₂: 30 min after T₁; T₃: 1 h after T₁; RR: respiratory rate; MValv: alveolar minute volume; VDalv: alveolar dead space volume; PetCO₂: end-tidal CO₂ partial pressure; VCO₂: CO₂ production; V_Te: expiratory tidal volume; V_Talv: alveolar tidal volume; SII: phase II slope of the capnogram; SIII: phase III slope of the capnogram; P_ECO₂: partial pressure of CO₂ in exhaled air; Intercept Y2: intersection between SII and the y axis; Intercept Y3; intersection between SIII and the y axis; P1V: volumetric capnography phase 1 volume; P2V: volumetric capnography phase 2 volume; PIF: peak inspiratory flow; PEF: peak expiratory flow; T_i: inspiratory time; T_e: expiratory time; P(a-et)CO₂: arterial to end-tidal CO₂ gradient; and CO: cardiac output.

Figure 1
A: representative curves of the volumetric capnography (volume × CO₂) at baseline (T₀, black) and at 1 h after the endpoint (T₃, red). B and C: representative curves of trends seen throughout the experiment. Figures obtained and adapted from the Analysis Plus software (Novametrix, Wallingford, CT, USA). T₀: baseline; T₁: endpoint; T₂: 30 min after T₁; T₃: 1 h after T₁; V₀ aw: anatomical dead space volume; End-Tidal CO₂: end-tidal expiratory pressure of CO₂; VCO₂: CO₂ production (mL/m); Airway dead space: anatomical dead space volume; MV, Alveolar spon: spontaneous alveolar minute volume; V_T, Alveolar spon: spontaneous alveolar tidal volume; Phase III Slope: phase III slope of the capnogram; Phase II Intercept: intercept of the phase II slope of the capnogram; Phase III Intercept: intercept of the phase III slope of the capnogram; Phase I Volume: volume of the phase I slope of the capnogram; and Phase II Volume: volume of the phase II slope of the capnogram.

This study was conducted in conjunction with the work published by Pereira et al.,³ which has been approved by the Ethics Committee on the Use of Animals of the State University at Campinas Institute of Biology (Reference no. 2298-1).

At baseline (T₀, before the clots were injected), all of the variables were measured. The clots were injected in increments of 5 mL until a borderline (i.e., “near-fatal”) mean pulmonary artery pressure (the primary endpoint) was reached. The mean quantity of clots injected was 24.7 ± 4.3 mL, and the mean clot injection time was 45 min. As can be seen in Table 1, gas exchange (PaCO₂) and hemodynamic changes (cardiac output) were evaluated at three different time points: T₁ (the endpoint), T₂ (30 min after T₁), and T₃ (1 h after T₁).

For the comparison between hemodynamic, gas exchange, and respiratory variables at T₀, T₁, T₂, and T_3, we used repeated-measures ANOVA (Winstat, version 3.1). Values of p < 0.05 were considered statistically significant.

PetCO₂, MValv, and the alveolar dead space volume presented significant differences among the various time points evaluated, whereas RR did not. It is well known that MPE leads to an increase in RR and in lung volumes. The increase in RR and in lung volumes can be evidenced by a significant increase in MValv, which, in turn, leads to alveolar washout and, as a consequence, to a significant decrease in PetCO₂. Another factor that contributed to the reduction in PetCO₂ was a significant decrease in pulmonary perfusion (resulting from a decrease in cardiac output). There was a significant increase in the volume of the alveolar dead space, which does not take part in gas exchange. Following the rationale of this variable behavior, the volumes of VCap phases I and II were obtained in mL and per respiratory cycle. Those volumes increased significantly over the study period.

Other variables were provided by VCap or associated with other variables: VCO₂; SII; SIII; VCO₂/V_Te; alveolar VCO₂/V_T; SII/exhaled CO₂ partial pressure (SII/P_ECO₂); SIII/P_ECO₂; SIII/PetCO₂; and SIII/V_Te. The expected decrease in VCO₂ at T₁ (p < 0.001 vs. T₀) can be attributed to the increase in MValv, as well as to a significant reduction in pulmonary blood flow (resulting from a decrease in cardiac output). There were also significant reductions in other metabolic variables, such as VCO₂/V_Te, and alveolar VCO₂/V_T.

With similar pathophysiologies, SII and SIII variables also presented significant variations (p < 0.0001). The SII represents removal of CO₂ from the alveoli, which are the most distal elements of the small airways. The SIII represents the elimination of CO₂ from most alveoli and, in normal organisms, its shape is similar to a plateau, with a slight upward slope. Higher SIII/V_Te and SIII/PetCO₂ values suggest structural damage in the peripheral and distal part of the lungs, which promotes this heterogeneous distribution of ventilation.^5,6 The same principle applies to the significant drop in the normalization of SII/P_ECO₂, SIII/P_ECO₂, SIII/PetCO₂, and SIII/V_Te (p < 0.0001 for all). Negative SIII values seem to be associated with vascular damage,^2,5 whereas an excessive increase in these values may be associated with airway damage (such as that occurring in bronchiectasis, cystic fibrosis, and COPD).^7,8

It was necessary to normalize VCO₂/V_Te, SII/P_ECO₂, SIII/P_ECO₂, SIII/PetCO₂, and SIII/V_Te, in order to allow them to be compared to the equivalent CO₂ excretion rates (P_ECO₂, PetCO₂, and V_Te, respectively).⁹

Other variables that are not usually described in the literature are intercept Y2 and intercept Y3 (both in mmHg), which indicate an increase or a decrease in the caliber of the conducting airways. These variables refer to the intersection of SII and SIII with the y axis of the VCap curve and represent a mathematical increase of the inclination of the slopes. Scheffzek et al.¹⁰ were able to verify that. In the present study, there was a significant variation in those two variables (p < 0.0001 for both).

In conclusion, recording, observing, and analyzing the behavior of the parameters of respiratory mechanics, especially VCap, made it possible to identify MPE. When carefully applied and analyzed, our results can make a major contribution to decreasing morbidity and mortality in patients presenting with a clinical profile suggestive of MPE.

Further studies of MPE, either experimental or clinical, are still needed. Such studies could broaden our knowledge of the disease and of its implications for the cardiopulmonary system.

REFERENCES

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Publication Dates

• Publication in this collection
  Nov-Dec 2018