Hypotension during onset of spinal anaesthesia is caused by a sympathetic block [1,2]. Resting sympathetic nervous activity increases and the baroreceptor reflex activity decreases with advancing age . These physiological changes explain the exaggerated reduction in arterial pressure after a sympathetic block in the elderly [4,5].
The incidence of hypotension during spinal anaesthesia in elderly patients varies from 27% to 80% [4,6,7] depending on the definition. Studies using thoracic electrical bioimpedance [4,8-10], transthoracic echocardiography  or pulmonary artery catheter  have shown that cardiac output (CO) is either maintained or slightly decreased during onset of spinal anaesthesia.
Unfortunately, the time intervals between the reported measurements in these studies are often several minutes, and the description of changes is more a start-to-end relation rather than a description of the dynamic changes. Knowledge of the CO may be important to guide the appropriate use of vasopressors to treat circulatory depression. A recent advance in measuring CO is the LiDCO™plus monitor (LiDCO Ltd, Cambridge, UK), which is comparable with pulmonary artery catheters in intensive care patients . This monitor allows beat-to-beat measurement of stroke volume (SV) and is therefore an early indicator of CO changes.
The aim of our study was to demonstrate CO changes during onset of spinal anaesthesia in elderly patients using this high time-resolution method. We hypothesized that onset of spinal anaesthesia was associated with a decrease in CO.
Danish Medicines Agency and the Local Ethics Committee approved the study, and written, informed consent was obtained from all subjects. Thirty-two consecutive patients, ASA I-III, aged 60 yr or older, scheduled for elective plastic or orthopaedic lower limb surgery under spinal anaesthesia were included. We excluded patients with body weight <40 kg, patients receiving lithium and those with aortic valve regurgitation.
Anxious patients were either premedicated with triazolam 0.125-0.25 mg or diazepam 10 mg given orally 1 h before anaesthesia. All patients with concurrent cardiovascular medication received their medication in the morning before surgery. Intravenous (i.v.) access was established and a 20-G catheter was inserted in the radial artery. None of the patients received prophylactic ephedrine or fluid preloading. The LiDCO™plus monitor was calibrated after injecting lithium chloride 0.3 mmol (St Thomas' Pharmacy Department, London, UK) in a peripheral vein . CO was determined from this indicator dilution as arterial blood passed through a lithium-sensitive sensor. After the calibration, the LiDCO™plus system measured CO and calculated haemodynamic parameters using a pulse wave algorithm. Spinal anaesthesia was performed as decided by the attending anaesthesiologist. Bupivacaine plain (5 mg mL−1 without glucose, Marcain®; AstraZeneca, Albertslund, Denmark) or bupivacaine hyperbaric (5 mg mL−1 with 80 mg mL−1 dextrose, Marcain®) was injected through either a 25- or a 27-G needle inserted between L3-4 or L4-5. After injection, patients were turned in the supine position. The placement of an epidural catheter for postoperative pain relief using the combined spinal-epidural technique was allowed. A 2 mL epidural bupivacaine test dose with epinephrine was given, but not until 5 min before termination of data collection. The sensory block level was assessed by a cold discrimination at 2 min intervals.
If the systolic arterial pressure (SAP) decreased below 90 mmHg, patient received ephedrine 5 mg i.v., saline 0.9% infusion was started and the study was terminated. Otherwise data collection continued until patients were ready for surgery, which was defined as the time when subarachnoid block was sufficient for the particular type of surgery. The patients were subsequently referred to the operation room.
Haemodynamic parameters were calculated every 10 s as averages of five LiDCO™plus recordings of adjacent heartbeats. If CO changed by more than 25% from one heartbeat to the next, this recording was considered an artefact and discarded. We defined relative hypotension as a decrease in mean arterial pressure (MAP) >25% and absolute hypotension as a SAP below 90 mmHg as recorded by Carpenter and colleagues .
The primary effect parameter was CO change from baseline at the end of data collection. Baseline was defined as the five LiDCO™plus recordings of heartbeats at the time of subarachnoid injection. We also compared patients post hoc according to the presence of high arterial pressure at the baseline, defined as SAP ≥ 160 mmHg, and development of a high sensory blockade, defined as a sensory block reaching the dermatomal level of T5 or above.
Patient characteristics are reported with median and range, haemodynamic changes with mean (SD). The changes from baseline were analysed with paired t-test using SAS for Windows, version 8.2 (SAS Institute Inc., Cary, USA). P < 0.05 was considered statistically significant. We considered a 1 L min−1 decrease in CO to be clinically relevant . We calculated that a total sample size of 32 patients would allow us to detect this CO reduction, expecting a SD of 1 L min−1 and a 5% Type 1 error risk with atleast 99% power. The calculation was based on a pilot study of five patients where a standard deviation of 1 L min−1 was found. Secondary analyses comparing groups were performed with non-parametric analyses.
Patient characteristics are presented in Table 1, one patient had atrial fibrillation and another had diabetes mellitus. Data collection ended after a mean of 17 min. Five patients required ephedrine after a mean of 11 min. Eight patients with epidural catheter received a 2 mL test dose and this resulted in an increase in heart rate (HR) in one patient, most likely as a consequence of intravascular misplacement of the catheter tip. In two patients, the subarachnoid block was not sufficient for surgery and they received a supplemental bolus of epidural bupivacaine. Recordings from the last three patients ended at that time, i.e. 13-17 min after the intrathecal injection. In total, 213 of 2 48 000 (0.1%) recordings were discarded as artefacts. The adjacent 10 s average replaced further 5% of data because of arterial blood sampling or positioning of the patient.
The relative CO and MAP changes during onset of spinal anaesthesia are illustrated in Figure 1. On average, CO decreased 8% (P = 0.02), MAP decreased 27% (P < 0.001) and systemic vascular resistance (SVR) decreased 23% when data collection ended (Table 2). CO initially increased 19% or 1.1 L min−1 on average (P < 0.0001) and reached a maximum after 7 min when MAP had decreased 12% and SVR decreased 27%. The average CO and MAP changes during the entire data collection were 1.9% and −16.8%, respectively. CO decreased 0.9 L min−1 in four patients receiving angiotensin-converting enzyme (ACE) inhibitors and increased 0.2 L min−1 in four other patients receiving β-blockers. At the end of data collection, the average stroke volume variation (SVV) increased from 8.4% to 13.9% (P < 0.0001) and pulse pressure variation (PPV) increased from 9.6% to 14.8% (P = 0.006).
MAP decreased continuously during the study period and 21 patients developed relative hypotension, but only seven had a SAP below 90 mmHg (Table 3). The changes in HR were minimal, and bradycardia (HR < 50 beats min−1) was seen in only one patient. The haemodynamic changes were not significantly related to premedication, bupivacaine dose 15 mg or above, baricity, patient position or use of epidural catheter.
Onset of spinal anaesthesia resulted in reduction in the CO, 0.5 L min−1 on average in elderly patients untreated with fluids or vasopressors. However, CO increased initially reaching a maximum 7 min after the subarachnoid injection. MAP decreased continuously throughout the study period, whereas HR remained virtually unchanged.
In accordance with our findings, an initial increase in CO during onset of spinal anaesthesia was recently found . This study in elderly patients demonstrated that smaller local anaesthetic doses resulted in a significant increase in CO, 2 min after subarachnoid injection. The final CO decrease in our study (8%) is in accordance with another study in elderly men with cardiac disease . These 15 patients with a median sensory block at T4 had a 33% decrease in MAP, 26% decrease in SVR and 10% decrease in CO, as determined by a pulmonary artery catheter. Other studies reported similar changes (10-20% decrease in CO or cardiac index) using thoracic electrical bioimpedance [8-10] or transthoracic echocardiography .
Using thoracic electrical bioimpedance, it was found that a decrease in SV in some elderly patients was compensated by an increase in HR . In our study, CO decreased as a result of reduced SVR and SV that were not compensated by an increase in HR. This, on one hand, may be explained by the impaired baroreceptor activity  and, on the other hand, by the more frequent β-blocker medication in the elderly. However, only four of our patients received β-blockers, and only one of these was unable to increase HR to compensate for a large CO reduction. The lack of HR response in our study is thus most likely to be caused by impaired baroreceptor activity.
The four patients receiving ACE inhibitors had a 0.9 L min−1 CO decrease, but this study was not powered to compare haemodynamic response and concurrent cardiovascular medication.
The initial CO increase in our study may be attributed to a reduction in arterial vascular tone, which preceded the reduction of venous return . Ageing and elevated sympathetic activity increase the SVR . At the time of the largest CO increase, on average 7 min after the intrathecal injection, SVR had decreased 27% in our patients. At the end of data collection, 10 min later, the decrease in SVR was 23%. Thus, we can assume that the initial increase in CO is caused by this large reduction in afterload. This is supported by findings when patients are compared according to hypertension at baseline. In 20 patients with hypertension at the baseline (SAP ≥ 160 mmHg), the initial increase in CO was 1.3 L min−1 vs. 0.8 L min−1 in the 12 patients with normotension at the baseline (P = 0.04). A moderate afterload reduction may thus be associated with increased CO in elderly hypertensive patients.
At end of data collection, we observed a large and significant increase in SVV and PPV. These results should be considered with caution since the patients were not mechanically ventilated, and changes in respiratory cycle during the study period may enhance inter-individual differences in SVV and PPV. However, this suggests that hypotension was caused by decreased venous return.
Further analysis of this study showed that eight patients with sensory block level T3-T5 had a 1.1 L min−1 decrease in CO vs. 0.3 L min−1 in the 24 patients with sensory block level T6-T12 (P = 0.10). This is in accordance with evidence that cardioacceleratory fibres are blocked when spinal anaesthesia involves higher thoracic levels . We must, however, emphasize that this is a post hoc analysis and the overall correlation of final CO change and sensory block level was poor (r = 0.24; P = 0.16). The change in HR was similar in these groups, so the larger decrease in CO may be a consequence of reductions in preload and central venous return rather than a blockade of cardioacceleratory fibres. The interpretation of these findings is furthermore limited by the large inter-individual differences in the assessment of sympathetic block from sensory block level and our sample size provided less than 50% power to detect the observed difference.
The incidence of hypotension in this study was 66% and 22%, when defined as a decrease in MAP > 25% and SAP below 90 mmHg, respectively. This compares well with previous findings in elderly patients [4,6,7], as well as with the study by Carpenter and colleagues . In their study, 33% of 952 patients had hypotension, defined as a SAP < 90 mmHg or a 10% decrease from baseline. Other investigations reported incidences of hypotension as low as 15%, when defined as a decrease in arterial pressure greater than 30% or a SAP below 85 mmHg  and 8% when defined as a decrease in MAP > 30% . In elderly patients, it was recently reported that 22 of 25 patients required treatment with ephedrine as a consequence of a decrease in SAP > 25% or SAP below 100 mmHg after spinal anaesthesia for hip repair .
The strength of our study is the high time-resolution of data, which may follow the haemodynamic changes during onset of spinal anaesthesia more closely than other methods. Although we observed a statistically significant reduction in CO from baseline, this reduction was smaller than the estimated reduction in our sample size calculation. Thus, we cannot conclude that spinal anaesthesia per se is associated with a clinically important reduction in CO. In the patients with high sensory blockade, we observed a trend towards a larger CO decrease. Although most of the observed changes in CO were often of minor clinical relevance, describing the CO changes every 10 s provides better knowledge of the underlying physiology of spinal anaesthesia.
One limitation of our study is that we did not control the final sensory block level. It is likely that the block would have been higher in some patients after 30 min . However, we did not wish to delay treatment of hypotension to 30 min after subarachnoid injection. We collected haemodynamic data representing onset of spinal anaesthesia, and not spinal anaesthesia together with fluid preloading, ephedrine, elevation of legs, etc. Spinal anaesthesia was performed as decided by the attending anaesthesiologist, who chose the dose and bupivacaine baricity, to achieve the optimal anaesthesia for the given patient and type of surgery. The placement of epidural catheter after subarachnoid injection was unlikely to influence haemodynamic or the sensory block level. No medication was given through the catheter, apart from a 2 mL bupivacaine test dose 5 min before termination of data collection.
Although cardiovascular medications and atrial fibrillation can influence haemodynamic responses, these do not necessarily impair the ability of using the LiDCO™plus, and we eliminated artefacts due to large beat-to-beat variation in pulse amplitude. Benzodiazepine premedication may be another limitation of our study. This may attenuate the arterial baroreflex [19-21]. However, premedication did not show a significant association with hypotension in another study of spinal anaesthesia . A total of 47% of patients had premedication.
We did not try to compare our CO measurements to a gold standard, but the purpose of this study was neither to evaluate the LiDCO™plus haemodynamic monitor nor to compare it with a pulmonary artery catheter. The LiDCO™plus monitor has been validated previously (limits of agreement from −26% to +21% when compared to thermodilution) and appears reliable without recalibration, for at least 8 h after cardiac surgery, a situation with frequent changes in arterial resistance [22,23].
This study shows that it is feasible to use the LiDCO™plus monitor to follow changes in haemodynamics at short intervals during onset of spinal anaesthesia. Future studies should include longer observation time. This will allow evaluation of different regimes to maintain haemodynamic stability.
In conclusion, biphasic changes in CO were observed during spinal anaesthesia in elderly patients using a method with high time-resolution. Initially, CO increased. Subsequently, it decreased significantly from baseline, although this decrease was of minor clinical importance.
The authors wish to thank The Danish Medical Research Council (Grant number: 22-04-0019) and Oberstinde Kirsten Jensa la Cour's foundation for supporting this research.
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