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The influence of different degrees of temperature of intrathecal levobupivacaine on spinal block characteristics in orthopedic surgeries: A prospective randomized study

1 Department of Anesthesia and Surgical Intensive Care, Faculty of Medicine, Mansoura University, Mansoura, Egypt
2 Department of Orthopedics, Faculty of Medicine, Mansoura University, Mansoura, Egypt

Correspondence Address:
Medhat Mikhail Messeha,
Department of Anesthesia and Surgical Intensive Care, Faculty of Medicine, Mansoura University, Mansoura, Mansoura
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/aer.AER_76_19


Background and Aims: The temperature of the local anesthetics may affect the distribution of spinal anesthesia. The aim of the current study is to compare the effects of different degrees of intrathecal levobupivacaine 0.5% on the spinal anesthesia characteristics and shivering in orthopedic surgery. Materials and Methods: A randomized, prospective, and controlled trial was conducted on 120 patients aged 40–70 years with American Society of Anesthesiologists Classes I and II and who scheduled for orthopedic surgery; they were randomly distributed into three groups: Group 1 (L 24°C) – levobupivacaine 0.5% warmed to 24°C; Group 2 (L 30°C) – levobupivacaine 0.5% warmed to 30°C; and Group 3 (L 37°C) – levobupivacaine 0.5% warmed to 37°C. Every patient had received 3 mL of 0.5% levobupivacaine intrathecally. Sensory blockade was tested using the loss of pinprick sensation, whereas the motor block was tested using the modified Bromage scale. The onset and grading of shivering after spinal anesthesia were recorded. Results: The use of intrathecal levobupivacaine 0.5% warmed to either 30°C or 37°C resulted in a significant acceleration of the onset of either sensory or motor blockade with a significant prolongation in the duration in addition to significant delay in the onset of shivering and the time of the first analgesia requirement in comparison to those of spinal anesthesia with levobupivacaine at room temperature (24°C). Notably, a nonsignificant difference in the spinal block characteristics and shivering was observed between Group L 30°C and Group L 37°C. Conclusion: The increasing the temperature of levobupivacaine 0.5% to 30 °C attains more rapid onset of sensory and motor blocks ,with prolongation of the onset of shivering. It could be considered as effective equivalent to warming levobupivacaine 0.5%to 37°C in spinal anesthesia.

Keywords: Levobupivacaine spinal block, orthopedic surgery, temperature

How to cite this URL:
Elsharkawy RA, Messeha MM, Elgeidi AA. The influence of different degrees of temperature of intrathecal levobupivacaine on spinal block characteristics in orthopedic surgeries: A prospective randomized study. Anesth Essays Res [Epub ahead of print] [cited 2019 Aug 18]. Available from:

   Introduction Top

Spinal anesthesia is the gold standard regional anesthetic technique used for lower limb orthopedic surgery.[1] The distribution of the local anesthetic agents (LA) used in spinal anesthesia is influenced by several factors such as viscosity and density of the injectate, which, in turn, is affected by the temperature.[2],[3] It has been reported that warming of the LAs up to 37°C enhanced the diffusion of the LA across the nerve membrane and subsequently rapid onset of sensory and motor blocks.[4],[5]

Levobupivacaine is the pure S enantiomer for racemic bupivacaine. It has a greater affinity for the plasma protein binding and lesser affinity for cardiac sodium channels. Consequently, the risk of central nervous system and cardiovascular toxicity could be reduced.[6],[7] Moreover, the plain levobupivacaine had a lower incidence of bradycardia and hypotension.[8] Because of these merits, levobupivacaine becomes an attractive substitute to bupivacaine.[9]

Shivering is a common adverse effect occurred due to spinal anesthesia with 55% incidence.[10] Besides the disruption of the comfort of patients, shivering has different hemodynamic changes, such as increasing the oxygen consumption, increasing the carbon dioxide production, and, therefore, increasing the cardiac effort.[11]

The current study was designed to compare the effect of different degrees of temperature of intrathecal 0.5% levobupivacaine on the characteristics of the spinal anesthesia and the shivering in orthopedic surgery.

   Materials and Methods Top

This prospective randomized study was carried out at Emergency Hospital, Mansoura University. The study enrolled 120 patients of either sex, aged 40–70 years, and American Society of Anesthesiologists physical status classes I and II who prepared to undergo elective repair of unilateral lower limb fracture under spinal anesthesia. The approval of this study was granted by the Institutional Research Board of Mansoura University with a code number R/18.11.340 and then was registered in the Clinical with the registry number NCT03790163. Written informed consent was obtained from every patient involved in the study.

Patient's refusal; pregnant women; patients with body mass index >35; multitraumatized patients; patients with coagulopathy, neuromuscular disorders, and psychiatric disorders; patients on opioid analgesic or opioid abuse; patients with a history of allergy to the anesthetic drug used and previous lumbosacral spinal surgery; patients with local skin infection or sepsis in the planned injection area; and patients with deformity in the vertebral column were excluded from the current study.

The eligible patients were randomly distributed by the computer-generated randomization table into three equal groups (n = 40) using a sealed envelope method. The sealed envelopes were opened by an anesthesiologist who was not participating in the study to prepare the spinal injectate solution according to the randomization.

In the first group (L 24°C), 3 ml of levobupivacaine 0.5% (Chirocaine 5 mg/ml, AbbVie, Italy) was warmed to 24°C in the incubator device (BT1020) for warming drug vials and syringes. In the second group (L 30°C), 3 ml of levobupivacaine 0.5% (Chirocaine 5 mg/ml, AbbVie, Italy) was warmed to 30°C for at least 24 h in the incubator device (BT1020) for warming drug vials and syringes. In the third group (L 37°C), 3 ml of levobupivacaine 0.5% (Chirocaine 5 mg/ml, AbbVie, Italy) was warmed to 37°C for at least 24 h in the incubator device (BT1020) for warming drug vials and syringes.

On arrival to the operating theater, standard monitoring including three-lead electrocardiogram, noninvasive blood pressure, and pulse oximetry was applied, and the basal vital signs were recorded. After securing a 20-G intravenous (IV) cannula, the preloading was given with 10 ml/kg Ringer's lactate. For standardization, all IV fluids were warmed to 37°C, and the room temperature was adjusted to 24°C.

Patients were informed with the methods of assessment of sensory and motor blocks before anesthesia. The spinal anesthesia, under complete aseptic precautions, was done in a sitting position in the L3–L4 intervertebral space with a midline approach, using a 22-G spinal needle. After confirmation of the free flowing of the cerebrospinal fluid (CSF), the prepared spinal injectate was given slowly according to group allocation without aspiration or barbotage. The intrathecal solutions were prepared by the anesthetist not involving the study and given to another anesthetist who performed the spinal anesthesia and did not know the exact temperature of the solution. Following the spinal anesthesia, the patient was turned immediately in a supine position and the anesthesiologist, who was unknown to the group allocation, tested the sensory and motor blocks.

The sensory block was assessed with pinprick method using a 25-G needle,[12] where score 0 means perception of sharp pain, score 1 means feeling touch sensation only, and score 2 means no sensation. The onset of sensory block was considered as the time interval from the completion of injection of prepared intrathecal solution and the recorded sensory block score 2 at the T6 dermatome. This was tested every 2 min. The duration of sensory block was determined as the time interval of the withdrawal of sensory loss within the two dermatomes segments.

The motor block was evaluated using the modified Bromage scale,[13] where 0 means the ability of the patient to move the hip, knee, and ankle; 1 means the inability of the patient to move the hip, but can move the knee and ankle; 2 means the inability of the patient to move the hip and knee, but can move the ankle; and finally 3 means the inability of the patient to move the hip, knee, and ankle. The onset of motor block was considered as the modified Bromage score is equal to 3. The complete recovery of the motor block was assumed when modified Bromage score is equal to 0. The duration of motor blockade was defined as the time interval from the complete motor blockade till the complete recovery of the movement of the knee and fingers.

The hemodynamic data were recorded basally before the intrathecal injection; just after the injection; 5, 15, 30, 60, 90, and 120 min intraoperatively; immediately after the end of the surgery; and 1 and 2 h postoperatively. Hypotension episode was known as any drop of the systolic blood pressure ≥20% from the preanesthetic value. If hypotension occurred, it was treated with a rapid infusion of 250 ml of crystalloid solution and/or incremental doses of IV ephedrine (3 mg). A clinically relevant bradycardia was known as a fall in the heart rate (HR) <50 beats/min and treated with incremental IV doses of 0.2 mg of atropine.

The shivering after spinal anesthesia was evaluated using a scale,[14] where score 0 indicates no shivering; score 1 indicates no visible muscle activity, but one or more of piloerection, peripheral cyanosis, or peripheral vasoconstriction; score 2 indicates the muscular activity noticed in only one muscle group; score 3 indicates moderate but not generalized muscular activity, which noticed in more than one muscle group; and score 4 indicates violent generalized muscular activity which involves the entire body. The onset time of shivering and its grading were noted and recorded.

Pain-free period was considered as the interval time from the onset of sensory blockade and the administration of the first dose of rescue analgesic.

Statistical analysis

The sample size calculation was done based on the equation of with the standard deviation (SD) of 20 and error rate of 4. The number of patients required for the study according to the calculated sample size was 96. However, because of the drop out cases may be considered 25%. So 120 patients were invited to this study.

Data were analyzed using SPSS version 20 (IBM, SPSS, version 21, Inc, Chicago, IL, USA). Kolmogorov–Smirnov test was done to test the normality of distribution of data. Quantitative data were described as mean ± SD, whereas qualitative data were described as frequency (%). All groups were compared using analysis of variance. Comparison between groups was done by post hoc test of Tukey. P < 0.05 was considered statistically significant.

   Results Top

One-hundred and thirty patients were assessed for eligibility in this trial. Six patients refused to sign the consent and four other patients did not fulfill the inclusion criteria. The remaining 120 patients completed the study as shown in [Figure 1].
Figure 1: Study flow diagram

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No significant differences were recorded between the three studied groups regarding demographic data, duration, and type of surgical procedure [Table 1].
Table 1: Demographic and surgical characteristics (n=40)

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The recorded hemodynamic changes (HR and mean arterial pressure [MAP]) showed no statistically significant difference between the studied groups either intraoperative or postoperative [Figure 2] and [Figure 3].
Figure 2: Heart rate (mean ± standard deviation). Group 1: L 24°C, n = 40; Group 2: L 30°C, n = 40; Group 3: L 37°C, n = 40

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Figure 3: Mean arterial pressure (mean ± standard deviation). Group 1: L 24°C, n = 40; Group 2: L 30°C, n = 40; Group 3: L 37°C, n = 40

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The onset time of the sensory block and the time required to reach the highest sensory level (T6) were statistically significant accelerated in patients of the L 30°C and L 37°C groups when compared with those of L 24°C group with a nonsignificant difference between Group L 30°C and Group L 37°C [Table 2].
Table 2: The characteristics of spinal block (n=40)

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Patients in Group L 30°C and L 37°C showed significant rapid onset of motor block, and the time needed to reach the maximum motor block was earlier in comparison to patients in the L 24°C group without a significant difference among Group L 30°C and Group L 37°C [Table 2].

The mean durations of the sensory block and motor block were significantly prolonged in Group L 30°C and L 37°C when compared with L 24°C with nonsignificant difference between Group L 30°C and Group L 37°C [Table 2].

The time for the first analgesic request was significantly delayed in patients in the L 30°C and L 37°C group when compared with the L 24°C group with nonsignificant difference between Group L 30°C and Group L 37°C [Table 2].

The onset of shivering was significantly earlier in Group L 24°C as compared to Group L 30°C and Group L 37°C with nonsignificant difference between Group L 30°C and Group L 37°C. No significant difference was observed between the incidence and the grading of shivering among the three groups [Table 3].
Table 3: The characteristics of shivering (n=40)

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   Discussion Top

The current study showed that increasing the temperature of 0.5% levobupivacaine to either 30°C or 37°C used for spinal anesthesia resulted in significant acceleration of the onset of both sensory and motor blockades with a significant prolongation of both blocks. Furthermore, warming of levobupivacaine to 30°C or 37°C caused a significant delay in the onset of shivering and the time of the first request of analgesia in comparison to spinal anesthesia with levobupivacaine at 24°C. Notably, a nonsignificant difference was observed in the spinal block characteristics and shivering between Group L 30°C and Group L 37°C.

The onset of either the sensory or the motor block was significantly earlier with the use of the intrathecal levobupivacaine warmed to 30°C or 37°C with a significant prolongation of both blocks in the present study. These results are in accordance with Aydin et al. who concluded that levobupivacaine when warmed to 37°C had a greater cephalad spread of sensory block assessed by the loss of pinprick sensation when injected into the subarachnoid space while the patient in the sitting position.[15] Furthermore, Nazli et al. reported that accelerated onset and prolongation of the sensory and motor blocks were noticed with the use of 0.5% levobupivacaine at 37°C versus 24°C in transurethral prostate resection operations.[16]

Similar result have been reported to those obtained in this current study as regard the effects of temperature on acceleration of the onset of either sensory or motor block.[4],[17],[18] Stienstra and van Poorten found that more rapid cephalic dissemination in a shorter time was seen in the spinal anesthesia when the bupivacaine 0.5% had been stored at 37°C.[19] Golboyu et al. concluded that, in cesarean operations when done under spinal anesthesia, increasing the temperature of bupivacaine to 37°C is a good method to provide rapid onset of sensory and motor blocks. In addition, it could decrease the incidence of shivering as well.[5] Meanwhile, Najafianaraki et al. found that there was no significant difference in the time to the highest sensory level, the maximum number of segment blockade, or the regression of sensory and motor blocks when used hyperbaric bupivacaine at 4°C and 23°C for spinal anesthesia for cesarean section.[20]

In vitro studies also showed that the effects of different temperatures of the local anesthetic solution on the density have features supporting the results obtained in the present study.[3],[21]

Another explanation of our results is the values of pka which is defined as the equality of the ionized and non –ionized fractions of local anesthetic (LA). By increasing the temperature, the pKa value decreases with an increase in the nonionized fraction of the LA to approach the physiological pH value.[22] Furthermore, Stoner had reported that the effect of increasing the temperature intensifies both the thermal and the kinetic energy which responsible for the motion of the individually mobile molecules of LA, leading to rapid spread, and extends the block inside the subarachnoid space.[23] Furthermore, the baricity, which is a measure of the relative density of the local anesthetic solution, may play an important role in the CSF level dissemination and duration of the effect of intrathecal anesthesia.[2] CSF density varies according to sex, age, pregnancy, and illness.[3] The distribution of LAs is affected by the change in temperature because the viscosity and density of all plain LAs may fall with every 1°C increase in temperature, causing more rapid cephalic dissemination.[4]

Hypothermia during regional anesthesia is contributed to three major factors: control inhibition of thermoregulatory center, heat loss to the environment, and body heat redistribution.[24],[25] The body temperature decreases and worsens during the administration of cold IV fluid or blood without warming,[26],[27] which affects the autonomic thermoregulatory, leading to vasoconstriction and shivering. Normally, during exposure to cold stress, core body temperature is maintained by vasoconstriction of the cutaneous vasculature to reduce heat loss and increases the metabolic heat production and shivering.

The present study showed that warming of levobupivacaine to 30°C or 37°C caused a significant delay in the onset of shivering, but did not affect the incidence or intensity of shivering. The average shivering incidence ranged between 50% and 55%. These results were in agreement with Crowley and Buggy who reported that the average shivering and hypothermia incidence rates related to neuraxial anesthesia in previous 21 studies were at the range of 40%–64%.[10] In conformity with Golboyu et al., the recorded incidence of shivering among the 37°C bupivacaine group was lower than those of 23°C bupivacaine group. The thermosensitive tissues within the spinal cord could be considered to contribute for the lower incidence.[5]

Autonomic thermoregulatory mechanisms significantly reduce the thresholds for shivering and vasoconstriction during spinal anesthesia.[28] When compared to general anesthesia, spinal anesthesia causes loss of heat only by redistribution of heat in the lower half of the body; however, the core body temperature do not remarkably decrease.[24],[28] Regardless of the cause of shivering, it has some undesirable effects of increased oxygen consumption (by 200%–500%) with decreased mixed venous oxygen saturation.[29],[30] Another deleterious effect of shivering is increasing the production of carbon dioxide due to the increase in muscular contraction and subsequently increase the production of lactic acid. Furthermore, catecholamine level is increased with shivering that leads to increase cardiac output, the left ventricle effort as well as mean ABP.[31]

Najafianaraki et al. reported that the low incidence of shivering among the bupivacaine at 23°C group than 4°C group in the application of spinal anesthesia for cesarean section, which might be due to an increase in the recorded blood pressure values and increased vasoconstriction, because the thermosensitive tissues of the spinal cord could be contribute to the shivering following neuraxial block.[20] In a study conducted by Crowley and Buggy, which had been supposed that the vasodilatation below the level of the blockage of the neuraxial block may be responsible for the redistribution of heat from the central compartment to peripheral compartment.[10]

The present study showed no statistically significant difference in hemodynamic changes (HR or MAP) between the studied groups either intraoperative or postoperative. In agreement with Nazli et al. who reported that no difference was observed between using levobupivacaine at room temperature and at 37°C for spinal anesthesia, regarding the incidence of hypotension and bradycardia.[16]

   Conclusion Top

Increasing the temperature of 0.5% levobupivacaine to 30°C achieves a more rapid onset of sensory and motor blocks, with prolongation of the onset of shivering. This is considered as effective equivalent to warming levobupivacaine 0.5%to 37°C in spinal anesthesia.

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   References Top

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  [Figure 1], [Figure 2], [Figure 3]

  [Table 1], [Table 2], [Table 3]


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