Hypotension is one of the most common complication of epidural (EA) and spinal (SA) analgesia resulting from arterial vasodilation rather than decreased venous return and cardiac output, leading to decreased vascular resistance (1–4).

It has been reported that during cesarean section (CS), hypotension following EA can occur in up to 80% of women (2–4); similar findings have also been noted in dogs (5–10). The consequences of low blood pressure affect both, the mother and unborn fetus. In the first place, epidural hypotension may be associated with nausea and the risk of vomiting in the mother. Additionally, rare cases can cause cardiovascular collapse, loss of consciousness, or aspiration of gastric content (if not intubated) (11). Furthermore, prolonged maternal hypotension can have deleterious effects on uteroplacental perfusion and subsequent acute fetal distress resulting in fetal hypoxia, bradycardia, and acidosis (12–16).

Previous studies have proposed multiple strategies for preventing hypotension after EA in pregnant women (17–33). Various combinations of fluid types, infusion rates, and timing were considered and tested with variable outcomes. Hence, optimal preventive strategies against hypotension during CS, are yet to be determined. Traditionally, crystalloid fluids have been administered before EA for CS (preload) (33, 34). However, some evidences suggested that the rapid redistribution of crystalloids from the vascular bed to the interstitial space makes this method not completely satisfactory (17–20, 29, 35). Therefore, a different approach was attempted with the administration of crystalloids at the point when the local block was about to start (coload). This approach improved the filling of the vasculature at the time of maximum vasodilation caused by the epidural or spinal blockade, and was therefore more effective in preventing hypotension (17–20). On the other hand, some authors noted that patients with colloid preload had fewer episodes of low blood pressure than those patients with colloid coloads (21, 22). In other studies, both groups were similarly hypotensive (23–27). In summary, in human medicine there is still no consensus on the type of fluid and its loading time in patients undergoing EA or regarding the total fluid and dosing rate in preventing epidural hypotension.

Interestingly, despite the similar risk of epidural-induced hypotension in veterinary and human patients, treatment strategies for dogs have received little attention until date. Bosman et al. studied colloid (HES 6%) loading in healthy, non-pregnant dogs (28). Fluids were administered at a constant infusion rate for 30 min prior to epidural administration of ropivacaine. Unfortunately, this strategy did not mitigate hypotension episodes in dogs. The main limitation of the present study was the small number of animals investigated therefore, future studies involving a larger study population and administration other types of fluids, different doses, and administration rates are needed.

During CS procedures, the risk of hypotension is high, and can be caused by anesthetic, sedative, and analgesic drugs, as well as the patient's dorsal recumbency during surgery, traction on ovarian pedicles, or sudden removal of the uterus from the abdomen. The combined effects of these factors can lead to severe hypotension. To minimize this risk, one of the recommended strategies is to avoid epidural-induced hypotension (16, 36).

Since there are no references to colloid/crystalloid preload or coload dosing in dogs and there is a wide variation in doses administered to humans, the authors decided to evaluate the effectiveness of crystalloid coload in preventing intraoperative hypotension in dogs undergoing CS and evaluate whether fluid administration would have a beneficial effect on newborn puppy outcomes evaluated based on the Apgar scoring system and umbilical cord blood gas results.

The mothers in both groups did not differ in terms of mean age, body weight, preoperative respiratory rate (RR), body temperature, dose of propofol required for the induction of general anesthesia, and number of pups per litter (Table 1). The baseline mean value of maternal heart rate (HR) for the two groups was comparable statistically. Furthermore, there was no statistically significant difference (p = 0.55) in the total anesthetic time (from the induction to the end of the surgery) between the control (53 ± 15.12 min) and treatment (55.22 ± 12.08 min) groups. Similarly, isoflurane demand was comparable in all investigated females (MAC 1.13 ± 0.19 vs. 1.22 ± 0.14, p = 0.41). No signs of fluid overload were observed in any of the mothers who received fluid coload.

Intraoperative parameters such as HR, RR, etCO2 and body temperature were also similar in all females. In contrast, blood pressure differed between the groups. In the control group, the mean values of SBP, DBP and MBP were 80.68 ± 7.29, 36.52 ± 8.75, and 52.30 ± 7.77 mmHg, respectively. Up to 91.6% of the investigated females developed hypotension, defined as a mean arterial pressure below 60 mmHg. In dams who received fluid coload, blood pressure was higher (101.46 ± 9.18, 48.01 ± 13.47 and 67.07 ± 13.15 mmHg for SBP, DBP, and MBP, respectively, p < 0.05) with significantly fewer episodes of hypotension (33%, n = 4).

Figure 1 shows the mean values of SBP, DBP and MBP tracings observed in the control and treatment groups during anesthesia for cesarean section. In both groups, SBP was the lowest after the removal of all puppies (T2), but in the treatment group blood pressure was significantly higher at this time point (T: 96.50 ± 24.05 vs. C: 76.98 ± 10.42 mmHg). A similar significant difference was noted for T1 and T3. The DBP did not change over time in all investigated females (p > 0.05), or between the investigated groups at all considered time points. In the treatment group, MBP dropped slightly from T1 (70.00 ± 20.67 mmHg) to T3 (64.47 ± 10.57 mmHg), nevertheless it was still higher than that in the control group at each of the investigated time points.

The number of puppies included in the study was 42 in the control group and 33 in the treatment group. Stillborn puppies and those with failed umbilical cord blood collection were excluded from the experiment. No differences were found in any umbilical blood gas parameters in the newborns of either group (Table 2). However, the neonatal viability assessment differed significantly, and the puppies in group T received higher scores in the 5-and 20-min assessments (Figure 2).

The present study, for the first time, showed the efficacy of crystalloid fluids coloading in dogs undergoing CS in preventing epidural-induced hypotension. Our results showed, that both SBP and MBP were significantly higher in the treatment group that received coload fluid treatment than those in the control group without additional fluid administration. Furthermore, episodes of hypotension were significantly less frequent in dams that received a fluid bolus (33 vs. 91.6%). Similar improvement in blood pressure have been widely reported in human medicine (17–20, 29). However, in the present study, similar to human reports, it was not possible to completely prevent episodes of maternal hypotension (17–20, 29). Nevertheless, we noted that the treated bitches, which received crystalloid coload at the same time as EA, had an overall higher blood pressure, and their newborns vitality scores at 5 and 20 min were also significantly better compared to the control group without fluid coload administration. Furthermore, in the treatment group, we observed an increase in HR at the first post-infusion point (T1). This observation can be explained by the Bainbridge reflex. According to this theory, the subsequent increase in venous return after rapid fluid infusion causes activation of the right atrial stretch receptors, triggering an increase in the HR (38). Such an effect might be beneficial for fetal circulation and welfare, and thus the subsequent newborn survival, since placental and fetal perfusion depends solely on maternal blood pressure (39).

We found that the investigated parameters of the umbilical cord blood gas analysis were similar in both the treatment and control groups. However, a comprehensive comparison of the obtained results poses some difficulty. Available data on the umbilical cord blood gas evaluation in dogs are limited. To the best of our knowledge, no reports have been published on the effect of maternal fluid infusion during anesthesia on newborn puppies' condition. Only human studies have reported no pH changes in umbilical cord blood after crystalloid or colloid preload administration to the mother before spinal anesthesia (32, 33, 40). In the present study, to assess neonatal outcomes, we measured not only umbilical cord pH, but also base excess and lactate concentration, as important markers confirmed in human medicine that indicate peripartum fetal stress. In the results presented, neither base excess nor lactate concentration showed differences between the investigated and control groups. Furthermore, pCO2, HCO3, and glucose levels were also similar in the T and C groups, and were comparable to those reported previously in dogs (5, 6). These data suggest that crystalloids infusion in dams at a rate of 15 mL/kg during EA might be ineffective for the improvement of umbilical blood gas in their newborn puppies.

Similarly, the blood gas parameters obtained indicated no differences in puppies' vitality immediately after delivery (AS at 0 min 2.2 ± 1.9 in the control vs. 2.6 ± 1.5 in the treatment group, p > 0.05). However, in the following evaluations of newborn vitality at 5 and 20 min, significant differences were found in AS between the treatment and control groups. The newborns of the treatment group had a higher AS both at 5 and 20 min than the puppies born from the dams of the control group (AS at 5 min: 6.7 ± 2.2 in the control vs. 7.9 ± 1.8 in the treatment group, p = 0.02; AS at 10 min: 8.3 ± 2.5 vs. 9.3 ± 0.9, p = 0.01). A possible explanation for this could be the results described by Hollmen et al. for humans (41). Babies in the group of lower maternal blood pressure after epidural analgesia had no or weak reflexes up to the 2nd day of life, compared to newborns of normotensive mothers, despite the similar initial ASs recorded in both groups. However, in most human investigations no differences in AS were observed (32, 33, 40) regardless of maternal blood pressure. Unfortunately, to date, no such study has been conducted in dogs. Similar to Hollmen et al. we found that, the differences in newborns' postnatal improvement between hypo- and normotensive dams were not apparent at the first post-delivery vitality assessment but they became evident over time. As explained by Hollmen et al. even short-term hypotension leads to decreased placental blood flow that persists for several minutes after the correction of maternal hypotension. Such a situation can cause neurological depression and abnormal postpartum neurological recovery.

The results presented here showed that crystalloids infusion, administered together with EA (coload), increased maternal blood pressure. Crystalloid coload was also beneficial for the vitality of the puppies and increased ASs at 5 and 20 min without a favorable effect on blood gas parameters. However, it was not possible to prevent maternal hypotension completely. Therefore, despite the administration of fluid bolus, maternal blood pressure should be carefully monitored throughout surgery and clinicians must be prepared for rescue hypotension treatment during CS.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

The animal study was reviewed and approved by Bioethics Committee of the Hirszfeld Institute of Immunology and Experimental Therapy. Written informed consent for participation was not obtained from the owners because this study included client-owned bitches scheduled for elective cesarean section. The cesarean section was decided independently of this research, solely on clinical indications (e.g., single pup pregnancy), the previous dystocia in history, or breed-related factors (brachycephalics).

AA: conceptualization, data collection, data evaluation, statistical analysis, and writing of the manuscript. MO: conceptualization, data collection, data evaluation, and reviewing and editing the paper. WN and ZK: supervising the study and reviewing and editing the paper. All authors contributed to the article and approved the submitted version.