Key-words: 0.45% sodium chloride solution - balanced salt solution - craniopharyngioma - diabetes
insipidus - hypernatremia
Introduction
Craniopharyngioma is a benign tumor that arises from squamous remnant of Rathke's
pouch and extends toward the hypothalamus. These patients commonly develop fluid and
electrolyte disturbances, notably Central Diabetes Insipidus and Syndrome of Inappropriate
Antidiuretic Hormone (SIADH) secretion during perioperative period. The immediate
postoperative period, is a state of hyperaldosteronism under the normal hypothalamic
pituitary axis.[[1 ]],[[2 ]],[[3 ]] Surgery for craniopharyngioma disturbs the normal hypothalamo-pituitary axis resulting
in electrolyte abnormalities. The fluid management during intraoperative period has
been found to influence the postoperative serum osmolality and serum sodium levels
significantly.[[4 ]] Hence, the optimal fluid management in perioperative period is essential to ensure
better patient outcomes.
Numerous previous studies have been done in animals demonstrating changes in serum
osmolality with infusion of large volume of hypo-osmolar fluids but evidence from
human studies is lacking. A previous study by Mukherjee et al.[[5 ]] comparing 0.45% saline, 5% dextrose and 0.9% sodium chloride in patients undergoing
craniopharyngioma surgery, reported significantly higher serum sodium levels in the
0.9% sodium chloride group as compared to 0.45% saline in the first 48 h postoperatively.
The use of normal saline was associated with higher incidence of hypernatremia, diabetes
insipidus (DI), and mortality (P = 0.05), while the group that received 5% dextrose
was associated with hyponatremia, hypoglycemia, and seizures.
There is no study till date which compared the use of balanced salt solution with
other fluids in patients undergoing craniopharyngioma excision. As Mukherjee et al.[[5 ]] have concluded that 0.45% sodium chloride solution is the ideal fluid for perioperative
use in patients with craniopharyngioma, so we planned to compare it with balanced
salt solution in patients undergoing resection of craniopharyngioma both in intra-
and post-operative period hypothesizing that intravenous infusion of balanced salt
solution will maintain osmolality better than 0.45% sodium chloride solution.
Methodology
A prospective randomized study was conducted after getting approval from Institute
Ethics Committee (NK/1577/MD10079-80) and was registered with Clinical Trials Registry
of India (CTRI) with Trial registry number of CTRI/2017/03/008159.
The study was conducted in patients undergoing transcranial resection of craniopharyngioma
after getting written informed consent from the patient or nearest kin. The patients
were allotted randomly into two groups by computer-generated random number table.
Patients in Group S (n = 15) received intravenous infusion of 0.45% sodium chloride
solution while patients in Group P (n = 15) received balanced salt solution (Plasmalyte
A) in the intraoperative and postoperative period till patients were started on oral
fluids. Patients undergoing transsphenoidal resection of craniopharyngioma, having
DI/Diabetes mellitus or renal abnormality before surgery were not included in the
study. In the preoperative period, demographic profile, presenting symptoms, neurological
and visual deficits, computed tomography (CT) and magnetic resonance imaging findings,
thyroid and cortisol level, Glasgow Coma Scale (GCS), serum and urine osmolality,
serum and urine sodium, urine-specific gravity, serum blood glucose level were recorded.
A standard anesthetic technique was followed in all the patients. Induction of anesthesia
was achieved with Propofol (1–2 mg/kg) with Fentanyl (2 μg/Kg) and muscle relaxation
was achieved by vecuronium 0.1 mg/kg. Anesthesia was maintained with isoflurane, oxygen-
nitrous oxide mixture (50:50) and intermittent doses of intravenous vecuronium 0.02
mg/kg. Ventilation was maintained with a fresh gas flow rate at 1-2 L/min and keeping
end tidal carbon-dioxide of 35–40 mm Hg. Intraoperative analgesia was maintained with
intravenous fentanyl infusion 1 μg/kg/h. Intraoperative monitoring also included invasive
blood pressure, capnography, central venous pressure (CVP), and urine output. Serum
sodium, urine sodium, urine and serum osmolality and urine specific gravity were measured
in the preoperative period, thereafter in intraoperative period once every hour for
first 3 h and then at the end of the surgery. CVP was maintained around 6–8 mm of
Hg and hourly urine output was measured during surgery. Standard anaesthesia protocol
for emergence from anaesthesia was followed in patients in whom elective postoperative
mechanical ventilation was not planned. The operating surgeon was asked about the
extent of tumor resection (partial or near total) at the end of the surgery.
As rescue measures, intravenous 0.45% sodium chloride solution was started in patients
who developed hypernatremia (serum sodium >145 mEq/L). Patients were monitored for
cerebral edema both clinically and by postoperative CT. Normal saline solution was
infused in patients who developed hyponatremia (serum sodium <135 mEq/L) in the intraoperative
period.
Patients were followed up in the postoperative period till they started taking fluids
and diet orally. They were evaluated daily for GCS, serum and urine osmolality, serum
sodium, and urine-specific gravity. Serum cortisol level was assessed on the 3rd postoperative
day. Serum and urine osmolality was estimated in the immediate postoperative period
to rule out polyuria due to administration of excessive intraoperative fluid. Patients
were investigated every day for the development of DI and requirement of vasopressin
to treat the same. Blood sugar levels were estimated regularly to exclude the possibility
of polyuria due to hyperglycemia.
If patients developed electrolyte disturbance in the postoperative period, it was
treated according to the institute protocol and rescue measures taken were noted.
According to the protocol if patient developed polyuria (UO >4 ml/kg/h) for two consecutive
hours, along with serum sodium >145 mEq/L then initially fluid intake was restricted
and serum sodium levels were assessed hourly. If the serum sodium levels still remained
high (>145 mEq/L) after 2 h, injection vasopressin 3U was given subcutaneously in
patient more than 14 years of age while injection vasopressin 2U (SC) was given to
children <14 years. If the patient developed hyponatremia (<135 mEq/L) postoperatively,
fluid intake of the patient was completely restricted for 2 h and serum sodium levels
was assessed hourly. If serum sodium level did not normalize after fluid restriction,
0.9% sodium chloride solution was administered such that the rise in serum sodium
levels did not exceed more than 0.5 mEq/L/h.
Statistical analysis
Statistical analysis was carried out using statistical package for social sciences
(SPSS Inc., Chicago, IL, USA, version 21.0). Continuous data were presented as mean
± standard deviation (SD) or median and inter quartile range, as appropriate. For
normally distributed data, two groups were compared using Student's t-test (unpaired).
For all skewed data, two groups distribution was compared using Mann–Whitney U test.
All normally distributed data were expressed as mean and SD. Skewed data were expressed
as median, interquartile range. Categorical and classified data were compared by Chi-square
test or Fischer's exact test. Repeated measure data were analyzed with repeated measures
analysis of variance with Bonferroni correction for comparison of two groups. Data
correlation was analyzed by Pearson's or spearman's correlation based on distribution
of data. A P < 0.05 was considered significant.
Results
Thirty patients were enrolled for the surgery. Three patients from group S were excluded
from the study after enrolment as the histopathology did not confirm the tumor to
be craniophayngioma. Two patients were excluded from group P as they developed intraoperative.
DI as intention to treat analysis. The observations were recorded and the results
were statistically analyzed for 13 patients in group P and 12 patients in group S
[[Figure 1 ]]. The demographic data, hormone status, intraoperative total intravenous fluid infused
were comparable in between the groups [[Table 1 ]]. The tumor size was comparable between the groups [[Table 1 ]]. All patients underwent near total resection of tumor.
Figure 1: Consort diagram
Table 1: Patient characterstics and intraoperative parameters
Serum osmolality was comparable between the groups in the preoperative period and
in the 1st h of surgery but the difference in serum osmolality was significantly different
in 2nd and 3rd h intraoperatively and at the end of surgery in between the groups
with higher values in patients who received balanced salt solution [[Table 2 ]]. We observed that the number of patients with serum osmolality more than 300 mosm/kg
were more in group P throughout the intraoperative period [[Table 2 ]]. In our study, postoperative day 0 (POD 0) a significant difference in serum osmolality
was observed among the two groups [[Table 2 ]].
Table 2: Serum osmolality (mOsm/kg) and serum sodium (mEq/L)
Serum sodium level in preoperative period was comparable in between the groups. Intraoperatively,
the difference in serum sodium levels was significantly higher in group P as compared
to group S at 3rd h and at the end of surgery although the values in both the groups
were within normal limits. Whereas in the postoperative period, values were higher
than in intraoperative period but were comparable in both the groups [[Table 2 ]].
Preoperative and intraoperatively urine osmolality and urine specific gravity were
comparable and within normal range in both the groups. Although urine osmolality was
lower in group S but the difference was not statistically significant. Urine output
and dose of vasopressin requirement during study period were recorded. Although the
urine output and vasopressin requirement were less in Group S, the difference between
the groups was not statistically significant [[Table 3 ]]. Time to start oral intake in postoperative period was also comparable in between
the groups, although oral intake was earlier in Group S.
Table 3: Urine output (ml/kg) and dose of vasopressin (units)
In this study, no patient developed any clinical features or had postoperative CT
finding suggestive of cerebral edema. Two patients (one adult and one child) from
Group P had developed DI in intraoperative period [[Table 4 ]]. All patients in both the groups developed DI in the postoperative period. In this
study population, one patient from group P died due to complication following intestinal
perforation attributed to steroid replacement. Rest all of the patients in this study
were discharged and among them, 66.6% in group P and 83.3% in group S had developed
chronic DI [[Table 4 ]].
Table 4: Complications and patient outcome
Discussion
In this study, infusion of 0.45% sodium chloride (osmolarity-154 mosm/L) was compared
to balanced salt solution (osmolarity- 294 mosm/L) in patients undergoing excision
of craniopharyngioma. We observed that the serum osmolality was comparable in 1st
h of surgery but the difference in serum osmolality was significantly different in
2nd h, 3rd h and at the end of the surgery in between the groups with higher values
of serum osmolality in patients receiving balanced salt solution. We also observed
that the number of patients with serum osmolality more than 300 mosm/kg were more
in patients receiving balanced salt solution. We observed significantly higher serum
osmolality on postoperative day 0 in patients receiving balanced salt solution. Though
there have been numerous studies in animal model demonstrating changes in serum osmolality
with infusion of large volume of hypo-osmolar fluid like ringer lactate but evidence
in human beings were lacking.
In a study conducted by William et al., a large volume (50 ml/kg) of hypo-osmolar
fluid (ringer lactate) and iso-osmolar (0.9% sodium chloride) fluid were given to
human volunteers and their effect on serum osmolality was compared. The authors concluded
that infusion of hypo-osmolar fluid ringer lactate causes transient decrease in serum
osmolality which normalized after 1 h of stopping of the infusion.[[6 ]] However, the results of this study done in healthy volunteers cannot be extrapolated
to patients with craniopharyngioma.
The difference in serum osmolality in between the two groups depends on the osmolarity
of fluids infused in intra- and posto-perative period. The main determinant of serum
osmolality is serum sodium that can be affected by sodium content of fluid which is
140 mEq/L and 77 mEq/L respectively in balanced salt solution and 0.45% sodium chloride
solution respectively.[[7 ]]
In this study, the infusion of 0.45% sodium chloride solution in intraoperative and
postoperative period in patients undergoing craniopharyngioma resection surgery was
associated with lesser fluctuations of serum sodium and less episodes of hypernatremia
whereas the use of balanced salt solution (plasmalyte A) is associated with higher
sodium values in both intra- and post-operative period. Three patients (two adults
and one child) who received 0.45% sodium chloride developed hyponatremia and required
change of fluid to 0.9% sodium chloride during intraoperative period.
Pratheesh et al. compared 0.9% sodium chloride, 0.45% sodium chloride and 5% dextrose
as perioperative fluids in patients undergoing craniopharyngioma surgery and observed
higher fluctuations in serum sodium levels in patients receiving 0.9% sodium chloride.[[8 ]] Mukherjee et al. in their study in patients of craniopharyngioma, found serum sodium
of 157.8 mEq/L in patients receiving 0.9% sodium chloride compared to 143.4 mEq/L
in those receiving 0.45% sodium chloride in the intraoperative period.[[5 ]]
In our study, serum sodium levels were higher but comparable in both the groups in
postoperative period as measured on POD 0, 1, and 2. We observed sodium levels from
145.6–146.6 mEq/L in patients receiving 0.45% sodium chloride as compared to 149.1–151
mEq/L in patients receiving balanced salt solution in the postoperative period. However,
Mukherjee et al.[[5 ]] observed significantly higher serum sodium levels varying from 148.6 to 159.2 mEq/L
in the 0.9% sodium chloride group as compared to 0.45% sodium chloride group varying
from 138 to 139 mEq/L in the first 48 h postoperatively. They suggested that the findings
may be due to difference in sodium content of the transfused fluids- 0.9% sodium chloride
(154 mEq/L), 0.45% sodium chloride (77 mEq/L).
Lehrnbecher et al. demonstrated wide fluctuations in serum sodium levels in the intraoperative
and postoperative period in patients who underwent resection of craniopharyngioma.
The authors used sodium free fluid in patients having polyuria and high sodium containing
fluid for patients who received desmopressin.[[9 ]] Wide fluctuation in serum sodium levels was not seen in our study as we used rescue
measures to manage hyper and hyponatremia including vasopressin to treat DI as compared
to this study.[[9 ]]
In our study, two patients belonging to balanced salt solution group had intraoperative
DI, one adult and one pediatric. Lehrnbecher et al. reported no correlation between
the extent of tumor resection and the incidence of DI in their study.[[9 ]] They explained that in addition to axonal damage by surgery, other factors including
alterations in blood flow, metabolic activity and individual variations influence
the extent of axonal degeneration which determine the occurrence of DI.[[10 ]] In our study, the tumor size in both the groups were comparable and near total
excision was done in all the cases, thus the size of the tumor resected may not be
the cause of intraoperative DI. However, Bucci et al. have observed direct correlation
between the incidence of DI with the extent of tumor resection.[[11 ]]
Patients undergoing resection of craniopharyngioma classically present with triphasic
pattern of DI-SIADH-DI in postoperative period. Classic triphasic pattern seen in
craniopharyngioma is characterized by initial phase of DI lasting for 24 h after surgery
followed by a second phase of inappropriate vasopressin leading to hyponatremia lasting
for 2–14 days and third phase of DI.[[12 ]] We could not demonstrate SIADH or triphasic pattern in our study. This could be
explained as DI was treated in our patients with vasopressin that induces temporary
oliguria.[[9 ]] In our study, only 55% of patients who underwent resection of craniopharyngioma,
developed DI in the immediate postoperative period. However, in study by Lehrnbecher
et al., all patients developed DI in postoperative period in <18 h, the reason for
which was not clear in their study.[[9 ]]
In our study population, only one patient died who belonged to group P. He died due
to complication following intestinal perforation attributed to steroid replacement
as the patient was hypocortisolic and was on continuous hydrocortisone replacement.
Rest all of the patients in our study were discharged and among them, 66.6% in group
P and 83.3% in group S were discharged with chronic DI.
Limitations
The number of patients included in our study was less as the study was time bound.
Result could be validated better if we could have included more patients of craniopharyngiomas.
Conclusion
We conclude that 0.45% sodium chloride solution is preferred over balanced salt solution
as serum osmolality and serum sodium were maintained better with 0.45% sodium chloride
solution infused in perioperative period in patients undergoing transcranial excision
of craniopharyngioma.
