Patients :
Forty-one patients were selected between January 2019 and March 2020. Six were excluded: five due to lack of recording and one due to preoperative doses of norepinephrine > 500 µg/h. Thirty-five patients undergoing neurosurgery or neuroradiology procedures were prospectively included: 27/35 (77%) patients underwent intracranial surgery, and 5/35 (14%) underwent spinal surgery. We had for intracranial surgery : 4 aneuvrism clipping, 9 meningioma removal, 8 single or multiple metastasis removal, 4 high grade tumor removal and 2 schwanomma removal. Main operation duration was 5h30. Spinal surgery was represented bay arthrodesis (4/5) of at least three stages. Patient characteristics are reported in Table 1.
Table 1
Caractéristiques | Patients totaux n = 35 |
Sexe féminin, n (%) | 25 (71) |
Age (ans) | 58 (52–66) |
Poids (Kg) | 70 (60–80) |
Taille (cm) | 165 (162–170) |
IMC (Kg/m2) | 25,7 (22–28) |
ASA, n (%) | |
I | 2 (6) |
II | 26 (74) |
III | 7 (20) |
Bas risque cardiovasculaire | 19 (54) |
FDR CV (%) | |
HTA | 11 (31) |
Tabagisme actif | 4 (11) |
Diabète | 1 (2) |
Dyslipidémie | 5 (15) |
Obésité | 3 (9) |
Insuffisance rénale | 1 (3) |
Antécédents (%) Traitements (%) | |
Cancer solide | 8 (23) |
IEC /ARA 2 | 5 (15) |
Inhibiteur calcique | 3 (9) |
Bêta bloquant | 3 (9) |
Diurétiques | 2 (6) |
Biologie | |
Hémoglobine pré-opératoire (g/dL) | 13,4 (12,4–14,6) |
Plaquettes (g/L) | 266 (176–256) |
Créatininémie (µg/L) | 67 (58–80) |
In those patients, we analysed 41 bolus and 33 continuous infusion sequences with complete recording of macrocirculation and microcirculatory devices. Every patient received at least one bolus, 6 patients received two boluses and no patient received more than two boluses. For videocapillaroscopy, 30 bolus sequences were analysed in 30 patients (5 recorded sequences presented insufficient quality), and only 9 sequences of continuous infusion were analysed (over 18 recorded), for the same reason (Fig. 1).
Time to reach maximal effect :
Concerning microcirculatory parameters, the maximal effect on MAP occurred 52 [47–55] seconds after the bolus. The time to reach the MAP plateau was 260 [160–303] seconds after continuous infusion started.
Macrocirculatory parameters :
Before bolus and continuous infusion, patients presented a median MAP of 67 (60–74) mmHg, a CO of 4,8 [3,2–6] L/min and an SV of 74 [49–86] mL, for an HR of 70 [61–77] pulse/min. Variations of pulsed pressure (ΔPP) was 10 [5–12] %.
Effects of a bolus of norepinephrine
Norepinephrine boluses were associated with a 30 [20–45] % increase in MAP (p < 0,0001) and a decrease in HR and SV of 6 [1–11] % (p < 0,0001) and 12 [4–16] % (p < 0,0001), respectively, leading to a decrease in CO of 15 [16–29] % (p < 0,0001). GALA increased by + 12 [6–15]° (p = 0,008) in median (Table 2).
Table 2
Bolus parameters evolution over time.
| Baseline | T15’ | T30’ | T45’ | T60’ |
MACROCIRCULATION | | | | | |
MAP (mmHg) | 68 (60–74) | 68 (61–77) | 72 (62–88)* | 79 (74–91)* | 89 (78–96)* |
HR (/min) | 70 (61–77) | 70 (62–77) | 70 (60–72) | 66 (60–72)* | 64 (58–71)* |
CO (L/min) | 4,8 (3,2–6) | 4,8 (3,1–5,7) | 4,6 (2,8 − 5,7)* | 3,9 (2,6 − 5,4)* | 3,9 (2,9 − 4,8)* |
SV (mL) | 74 (49–86) | 70 (46–82)* | 70 (42–75)* | 62 (42–75)* | 58 (43–71)* |
GALA (°) | 40 (26–47) | | | | 46 (35–64) |
MICROCIRCULATION | | | | | |
LASER DOPPLER | | | | | |
TPU | 6,3 (3,7–11,7) | 7,3 (3,9–11,6) | 6,9 (4,4–12,2)* | 6,9 (4,2–10,6) | 6 (3,7–11,5) |
PHOTOPLETHYSMOGRAPHY | | | | | |
PI (finger) (%) | 5,7 (3–8,7) | 5,9 (3,1–8,2) | 5,7 (2,8–8,3)* | 5,3 (2,5–7,8)* | 5,1 (2–7,8)* |
PI (ear) (%) | 1,4 (0,6 − 1,9) | 1,4 (0,6 − 1,9) | 1,4 (0,6 − 1,9) | 1,1 (0,6 − 1,8) | 1,2 (0,7 − 1,9) |
NIRS | | | | | |
StO2 (%) | 87 (82–89) | 87 (83–88) | 87 (83–88) | 87 (83–88) | 87 (82–88) |
THI (%) | 12,2 (10,4–13,7) | 12,3 (10,5–13,6) | 12,4 (10,4–13,6) | 12,5 (10,4–13,6) | 12,5 (10,3–13,7) |
TISSULAR CO2 (mmHg) | 40 (34–43) | 39 (34–43) | 40 (34–43) | 40 (34–43) | 40 (34–43) |
VIDEOCAPILLAROSCOPY | | | | | |
MFI | 2,16 (1,72 − 2,64) | | | | 2,06 (1,66 − 2,4) |
TVD (mm2/mm2) | 14,1 (11,9–16,1) | | | | 13,9 (11,7–15,4) |
Data are expressed in median (IQR). MAP = mean arterial pressure ; HR = heart rate ; CO = cardiac output ; SV = stroke volume ; GALA = global afterload angle ; TPU = tissue perfusion unit ; PI = perfusion index ; MFI = microvascular flow index ; PPV = percentage of perfused vessels ; StO2 = tissular saturation in O2 ; THI = tissular haemoglobin index ; TVD = total vessel density. (*) = p < 0,05. |
Effects of a continuous infusion
Norepinephrine continuous infusions were associated with a median increase of 23[12–34]% in MAP (p < 0,0001). This was coupled with a drop in HR of -10[-14–6]% (p < 0,001) but not in SV, in which variations remained nonsignificant (+ 2[-7-+4]%). However, a significant decrease in CO was observed, of 7 [0–14] % (p < 0,0001). GALA increased by + 7 [3–12]° (p = 0,007). (Table 3)
Table 3
Continuous infusion parameter evolution over time.
| Baseline | T15’ | T30’ | T45’ | T60’ | T180’ | T300’ |
MACROCIRCULATION | | | | | | | |
MAP (mmHg) | 66 (60–74) | 69 (58–78) | 68 (58–77) | 69 (58–78) | 70 (59–80) | 79 (76–98)* | 83 (77–98)* |
HR (/min) | 61 (55–72) | 61 (54–73) | 61 (55–73) | 60 (55–72) | 59 (54–68) | 58 (55–64)* | 57 (55–61)* |
CO (L/min) | 4,2 (2,9 − 6) | 4,2 (3–5,8) | 4,1 (2,9 − 5,7) | 4,1 (3,1–5) | 4,1 (3–4,5) | 3,8(3–5,8)* | 3,9 (3–5,6)* |
SV (mL) | 64 (46–81) | 64 (46–80) | 64 (45–78) | 65 (46–82) | 64 (43–68) | 62 (45–74) | 61 (44–76) |
GALA (°) | 40 (35–69) | | | | | | 43 (37–59) |
MICROCIRCULATION | | | | | | | |
LASER DOPPLER | | | | | | | |
TPU | 7,1 (1,8–13,4) | 7,2 (1,9–13,4) | 7,2 (1,9–13,4) | 7,0 (1,9–14,3) | 7 (2,1–14,7) | 7,1 (4,4–14) | 7,1 (4,5–12,6) |
PHOTOPLETHYSMOGRAPHY | | | | | | | |
PI (finger) (%) | 5,5 (3,2–8,3) | 5,3 (2,1–7,8) | 5,2 (2,1–7,8) | 5,1 (2–8,1) | 5 (2,2–8,3) | 5,9 (3–8,3) | 6,4 (3,3–8) |
PI (ear) (%) | 1,4 (0,6 − 1,9) | 1,4 (0,6 − 1,9) | 1,4 (0,6 − 1,9) | 1,4 (0,6 − 1,8) | 1,4 (0,7 − 1,9) | 1,8 (0,8 − 2,1) | 1,8 (0,8 − 2,1) |
NIRS | | | | | | | |
StO2 (%) | 87 (82–90) | 88 (83–90) | 88 (82–89) | 88 (82–89) | 88 (84–89) | 85 (82–89) | 85 (82–89) * |
THI (%) | 12,6 (10,5–14,1) | 12,4 (10,6–14,1) | 12,4 (10,6–14) | 12,5 (10,5–14) | 12,4 (10,4–13,8) | 12,1 (9,5–13,3) | 12,5 (9,9–13,8) |
TISSULAR CO2 (mmHg) | 40 (34–43) | 39 (34–43) | 40 (34–43) | 40 (34–43) | 40 (34–43) | 39 (33–43) | 39 (33–43) |
VIDEOCAPILLAROSCOPY | | | | | | | |
MFI | 1,8 (1,7 − 2) | | | | | | 2,1 (1,8 − 2,4) |
TVD (mm2/mm2) | 15,1 (14,1–15,5) | | | | | | 17,4 (15,6–18,7) * |
Data are expressed in median (IQR). MAP = mean arterial pressure ; HR = heart rate ; CO = cardiac output ; SV = stroke volume ; GALA = global afterload angle ; TPU = tissue perfusion unit ; PI = perfusion index ; MFI = microvascular flow index ; PPV = percentage of perfused vessels ; StO2 = tissular saturation in O2 ; THI = tissular haemoglobin index ; TVD = total vessel density. (*) = p < 0,05. |
Comparison between bolus and continuous infusion at peak of MAP
For a smaller (but nonsignificantly different) increase in MAP (p = 0,07), continuous infusion was associated with a more limited decrease in CO of 0,6 L/min (p < 0,001). As changes in HR were similar, this implies that differences in CO were attributed to differences in the decrease in SV. Indeed, we observed a smaller decrease in SV of 4 ml (p = 0,009). This was associated with a smaller increase in the GALA of 7° (p = 0,04). The results are exposed in Table 4 and Fig. 2.
Table 4
Comparison between bolus mode and continuous infusion : maximal effect for each.
| BOLUS | CONTINUOUS INFUSION | p |
MACROCIRCULATION | | | |
MAP (mmHg) | + 21 (15 ; 30) | + 16 (9 ;26) | 0,07 |
HR (/min) | − 8 (-12 ; -6) | − 7 (-10 ; -4) | 0,2 |
CO (L/min) | − 1,5 L (-1,1 ; -2,4) | − 0,9 (-1,5 ; -0,2) | < 0,001 |
SV (mL) | -11 (-8 ; -20) | − 7 (-13 ; -3) | 0,009 |
GALA (°) | + 12 (6–15) | + 7 (3–12) | 0,04 |
MICROCIRCULATION | | | |
PHOTOPLETHYSMOGRAPHY | | | |
PI (finger)(%) | -12 (-24 ; 0) | + 12 (4–20) | 0,008 |
VIDEOCAPILLAROSCOPY | | | |
MFI | -0,1 (-0,24 ; -0,06) | + 0,3 (0,1 − 0,4) | 0,03 |
TVD (mm2/mm2) | -0,2 (-0,2 − 0,7) | + 2,3 (1,5 − 3,2) | 0,002 |
PVD (mm2/mm2) | -0,36 (-1,5 ; -0,8) | + 1,44 (-0,7 ; +3) | 0,01 |
MAP = mean arterial pressure; HR = heart rate; CO = cardiac output; SV = stroke volume; GALA = global afterload angle; TPU = tissue perfusion unit; PI = perfusion index; MFI = microvascular flow index; PPV = percentage of perfused vessels; TVD = total vessel density; PVD = perfused vessel density. |
Microcirculatory parameters :
Intra- and interindividual variability for the assessment of the MFI score was good, with kappa coefficients of concordance of 0.82 and 0.87, respectively (p < 0.05).
Effect of a bolus of norepinephrine (Table 2)
Norepinephrine boluses led to a downward but not significant trend in MFI from 2,16 [1,72 − 2,64] to 2,06 [1,66 − 2,4] (p = 0,09) and TVD from 14,1 [11,9–16,1] to 13.9 13,9 [11,7–15,4] (p = 0.22). This was associated with a significant decrease in PI of -12 [0–24,9] % (p = 0,006). Concomitantly, we observed an early and transient increase in TPU at T30s (+ 14 [2,2–26,9] % (p = 0,003)). No significant variation concerning the remaining parameters was observed.
Effect of a continuous infusion (Table 3)
Norepinephrine continuous infusions were associated with an upwards but nonsignificant trend in MFI from 1,8 [1,7 − 2] to 2,1 [1,8 − 2,4] (p = 0,07) and a significant increase in TVD from 15,1 [14,1–15,5] to 17,4 [15,6–18,7] mm2/mm2 (p = 0,007). Concomitantly, PI also increased but not significantly by + 12 (4–20)%. In contrast, we observed a decrease in StO2 at thenar eminence (p = 0,03).
Comparison between bolus and continuous infusion at peak of MAP
bolus and continuous infusion showed overall opposite variations in microcirculatory parameters, as MFI (-0,1(-0,24;-0,06) vs. +0,3(0,1 − 0,4), p = 0,03), PI (-12(-24;0) vs. +12(4–20)%, p = 0,008), TVD (-0,2(-0,2 − 0,7) vs. +2,3(1,5 − 3,2)mm2/mm2, p = 0,002), for bolus and continuous infusion, respectively. The results are exposed in Table 4 and Fig. 2.