Results
Patient Characteristics
Of the 33 patients recruited, we were able to administer both phenylephrine and ephedrine and finish all measurements before surgical incision in 29 patients [20 males, 9 females, age 59 (13) yr, height 173 (9) cm, weight 77 (13) kg]. Among the 29 patients, 10 were ASA I, 12 ASA II, and 7 ASA III. Detailed patients characteristics and planned surgeries are described in Supplementary Table S1. In 13 patients, phenylephrine was given as the first treatment and ephedrine as the second treatment. In 16 patients, ephedrine was given as the first treatment and phenylephrine as the second treatment. The interval between the first and the second treatments was 20 (14) min. In two patients, we did not administer phenylephrine or ephedrine because changes in MAP after anaesthesia induction did not meet the predefined criteria. In another two patients,data were not analysable because of strong signal interference.
Responses to Phenylephrine Bolus Treatment
An example of changes in MAP, CO, and
after a typical first phenylephrine treatment is illustrated in Figure 1a–c, respectively. MAP increased from the pretreatment level of ≈70 mm Hg to the highest level of ≈110 mm Hg within 1 min after phenylephrine administration. At the same time, CO decreased from the pretreatment level of ≈8 litre min to the lowest level of ≈2 litre min, and
decreased from the pretreatment level of ≈65% to the lowest level of ≈58%. The measurements of MAP, CO, and
before and after phenylephrine treatment for every patient are presented in Figure 2a–c, respectively.
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Figure 1.
Continuous MAP, CO, and
recordings from two selected patients. (a–c) Recordings during phenylephrine treatment. (d–f) Recordings during ephedrine treatment. Both agents were given during the first treatment. Vertical arrows indicate the drug administration time.
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Figure 2.
Measurements of MAP, CO, and
for every patient. (a–c) Measurements before (pre) and after (post) phenylephrine treatments. (d–f) Measurements before (pre) and after (post) ephedrine treatments.
Grouped responses after the first and the second phenylephrine treatments are summarized in Table 1. MAP was consistently increased after the first [▵MAP=29.5 (9.3) mm Hg, P<0.001] and the second [▵MAP=42.6 (15.7) mm Hg, P<0.001] phenylephrine treatments. CO was significantly decreased after the first (▵CO=−1.7 (1.0) litre min, P<0.001) and the second (▵CO=−2.3 (1.7) litre min, P<0.001) phenylephrine treatments.
was also significantly decreased after the first (▵
=−4.9 (2.8) %, P<0.001) and the second (▵
=−1.8 (2.4) %, P<0.01) phenylephrine treatments. However, the difference in
decreases between the first and the second phenylephrine treatments was significant (P<0.01; Fig. 3).
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Figure 3.
Grouped MAP (a), CO (b), and
(c) changes after the first and second phenylephrine (Phe) and the first and second ephedrine (Eph) treatments. The blue bars represent pretreatment values; the green striped bars represent post-treatment values. *P<0.01 (first treatment vs second treatment, unpaired Student's t-test).
Changes in
correlated well with changes in CO after the first (r=0.74, P=0.004) and the second (r=0.67, P=0.005) phenylephrine treatments (Fig. 4b), but only weakly correlated with changes in MAP after the first (r=0.40, P=0.17) and the second (r=0.48, P=0.06) phenylephrine treatments (Fig. 4a).
(Enlarge Image)
Figure 4.
Pearson's correlations between
and global haemodynamics (MAP and CO) during the first and second phenylephrine (a and b) and the first and second ephedrine treatments (Tx) (c and d). ▵=post–pre.
Responses to Ephedrine Bolus Treatment
An example of changes in MAP, CO, and
after one of the first ephedrine treatments is illustrated in Figure 1d–f, respectively. MAP increased from the pretreatment level of ≈50 mm Hg to the highest level of ≈80 mm Hg within 2 min after ephedrine administration. However, CO remained unchanged at ≈5 litre min and
remained unchanged at ≈62%. The measurements of MAP, CO, and
before and after ephedrine treatment for every patient are presented in Figure 2d–f, respectively.
Grouped responses after the first and second ephedrine treatments are summarized in Table 1. MAP was consistently increased after the first [▵MAP=24.1 (13.5) mm Hg, P<0.001] and the second [▵MAP=28.3 (13.3) mm Hg, P<0.001] ephedrine treatments. CO was slightly, but insignificantly, increased after the first [▵CO=0.5 (1.7) litre min, P=0.15] and the second [▵CO=0.4 (0.9) litre min, P=0.28] ephedrine treatments. The changes in
were also insignificant after the first [▵
=−0.4 (2.3)%, P=0.11] and the second [▵
=0.5 (1.1)%, P=0.54] ephedrine treatments. The difference in
changes between the first and second ephedrine treatments was not significant (P=0.19) (Fig. 3).
Changes in
correlated with changes in CO after the first (r=0.84, P<0.001) and the second (r=0.68, P=0.01) ephedrine treatments (Fig. 4d), but very weakly correlated with changes in MAP after the first (r=0.24, P=0.38) and the second (r=0.39, P=0.18) ephedrine treatments (Fig. 4c).
Associations between
and Physiological Covariates (Pooled Data)
We first fitted a linear-mixed model to examine the effects of treatment and carryover on
. Our results showed that the treatment effect on
was significant (P<0.001) and that the carry-over effect on
was not significant (P=0.11). After adjusting the effects of treatment and carryover on
, linear-mixed models showed that there were significant associations (in the order of significance from high to low, data available upon request) between
and CO (P<0.001), between
and SV (P<0.001), between
and HR (P<0.001), between
and MAP (P<0.001), and between
and
(P<0.01); however, there were no significant associations between
and
(P=0.60) and between
and BIS (P=1.0). After taking CO into consideration, SV (P=0.85), HR (P=0.95), MAP (P=0.48), and
(P=0.64) were no longer significantly associated with
. Further analysis showed that the associations between CO and SV (P<0.001), between CO and HR (P<0.001), between CO and MAP (P<0.001), and between CO and
(P<0.001) were all significant.