www.esict.org

ISSN 1687-4056

Volume 8 Number (2)

September 2018

EJICT

Official Journal of The Egyptian Society

of Intensive Care & Trauma

Egyptian Journal

of

INTENSIVE CARE

& Trauma

ESICT BOARD

President

Hussein Sabri, FRCAAin Shams University

Vice President

Ibrahim Abdel-Ghany, MDAin Shams University

Secretary General

Mohamad Ismail, MDAin Shams University

Treasurer

Mohamad Elfekky, MDAlazhar University

Members

Alaa Koraa, MDAin Shams University

Gamal Elewa, MDAin Shams University

Sherif Wadea, MDAin Shams University

Adel Mohamad Alansary, MDAin Shams University

Maged Salah, MDCairo University

Adel Abdel-Fattah, MDCairo Unversity

Ahmad Saeed Okasha, MDAlexandria University

Inas Kamel, MD Cairo University

Tawfeek Noor Eldin, MDAlazhar University

Raafat Abdel-Azim, MDAin Shams University

Ameer Salah, MDAin Shams University

Amr Mattar, MDCairo University

Mohamed A. Moneim Bakr, MD Assuit University

Editor in Chief

Hussein Sabri, FRCAAin Shams University

Associate Editors

Alaa Koraa, MDAin Shams University

Gamal Elewa, MDAin Shams University

Sherif Afifi, MDNorth Western University USA

Adel M. Alansary, MDAin Shams University

Advisory Board

EJICT Editorial Board

EJICT 2018, Vol. 8 No. (2): September www.esict.org

INDEX Content Page

THE EFFECT OF USE OF ANIDULAFUNGIN IN FAILURE OF WEANING DUE TO UNRESOLVED VENTILATOR ASSOCIATED PNEUMONIA IN CONTUSED LUNGS Mohamed Gaber Ibrahium Allam

1-11

KETAMINE-PROPOFOL COMBINATION VERSUS PROPOFOL IN ISOLATED HEAD TRAUMA PATIENTS Omar Waguih Abbas - Nasser Ahmed Fadel - Hesham Abdelwahab Abo Eldahab Safinaz Hassan Osman - Mohamed Mahmoud Mohamed Mahmoud

12-23

SERIAL DETERMINATION OF BLOOD LACTATE/PYRUVATE RATIO AND SEQUENTIAL ORGAN FAILURE ASSESSMENT SCORE CAN PREDICT SURVIVAL IN PATIENTS WITH SEPSIS AND SEPTIC SHOCK Mohammad A. Algendy, Rami M.Wahba

24-35

COMPARATIVE STUDY BETWEEN CUFF LEAK TEST AND LARYNGEAL ULTRASOUND IN PREDICTING POST EXTUBATION STRIDOR Yousry Elsaied Rezk, Moataz Elsahat Rezk, Ahmed Hamdy Abdelrahman, Yehya Zakaria Gouda

36-41

EFFECT OF HYPOPHOSPHATEMIA ON THE OUTCOME OF PATIENTS WITH ACUTE EXACERBATIONS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE Atef Elrifai, Mokhles Abdel Fadil Zineldin, Tarik Saber Sarhan

42-48

TECHNIQUES FOR PERIOPERATIVE ANALGESIA FOR LIVE LIVER DONORS: PROSPECTIVE, RANDOMIZED CONTROLLED TRIAL Rasha S Bondok, Marwa A K Elbeialy, Rania M Hussien, Sabah NB Ayoub

49-59

Omar Waguih Abbas et al

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KETAMINE-PROPOFOL COMBINATION VERSUS PROPOFOL IN ISOLATED HEAD TRAUMA PATIENTS

Prof. Dr. Omar Waguih Abbas - Prof. Dr. Nasser Ahmed Fadel - Dr. Hesham Abdelwahab Abo Eldahab- Dr. Safinaz Hassan Osman - Dr. Mohamed Mahmoud Mohamed Mahmoud Lecturer of anesthesia, faculty of medicine, Cairo University

Aim and background: Traumatic brain injury (TBI) is a leading cause of death and severe neurologic disability. Propofol commonly used for induction of anesthesia decreases ICP (intracranial pressure) and CPP (cerebral perfusion pressure) as well, increasing risk of secondary brain injury. Our objective was to study the effect of ketamine – Propofol combination (ketofol) assuming it will decrease ICP while preserving cerebral perfusion pressure (CPP) in head trauma patients.

Methods: Forty patients with isolated head trauma were included in this study. Patients aged 20-50 years, ASA I and II, GCS 13, were randomly allocated in one of two groups; group K received ketofol (1:1) ratio as induction agent for anesthesia 1mg/kg ketamine plus 1mg/kg propofol and group P received Propofol 2mg/kg. Intracranial pressure, cerebral perfusion pressure, arterial blood pressure, and heart rate were recorded in these patients as well as any complication (e.g. postoperative nausea and vomiting). Time to recovery was also recorded for patients in both groups. Results: ICP was significantly reduced in both groups more in Propofol group (baseline in ketofol group was16.95±33, decreased significantly after 4 min post induction to 15.45±2.8, increased significantly at intubation and then decreased significantly again at 4 min after intubation to 15.9±2.51, while in Propofol group baseline was 16.60±1.67 decreased significantly 4 min after intubation to 12.50±1.28 , increased at intubation but still less then baseline and then decreased significantly again at 4 min post intubation to 14.1.±1.29). CPP increased significantly in ketofol group in comparison to Propofol group with significant difference at induction , 2 and 4 min post induction and significantly higher CPP in ketofol group in comparison to baseline at all points of measurement. Vital signs were significantly reduced in Propofol group in comparison to ketofol group. No statistically significant differences between both groups as regard time to recovery or complications. Conclusion: Ketofol (1:1) combination is a safe, effective alternative induction agent in isolated head trauma as it decreased ICP and preserved ABP; thus maintained higher CPP in comparison to propofol. Key words: (ketofol -Propofol-Head Trauma-Intracranial Pressure)

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Introduction Traumatic brain injury (TBI) is a considerable cause of death and severe disability. TBI may be divided into 2 types; Primary brain injury which is the injury occurring as a direct result of trauma; secondary brain injury which is any subsequent injury to the brain after the initial insult. Causes include: systemic hypotension (with decrease cerebral perfusion pressure), hypoxia, elevated intracranial pressure (ICP). (1) Several studies evaluated the effect of anesthetic techniques on neurologic outcomes in traumatic brain injury. (2) Principles of management include optimization of hemodynamic variables, selection of appropriate anesthetic technique and analgesic strategies that guard against secondary ischemic brain insults. (3)

In hemodynamically unstable patients, Ketamine is considered a proper induction agent of anesthesia, and particularly useful in TBI patients as hypotension has detrimental effect in these patients.(4.5.6.7.8) For long ketamine was not used in patients with traumatic brain injuries due to the fear of increasing intracranial pressure (ICP).(9, 10) later, a number of published studies proved that the use of ketamine was safe in patients with elevated ICP if these patients were mechanically ventilated or if used with conjunction of other anesthetic agents. Other studies suggested that ketamine acting as a NMDA receptor antagonist may confer neuroprotective effects. (11, 12) Propofol on the other hand has a neuroprotective effect through decreasing the cerebral metabolic rate for Oxygen (CMRO2). It also inhibits the glutamates release through decreasing NMDA receptors activation and it activates GABA – A receptor function that antagonizes the detrimental effect of acute brain injury. (13) However one of its side effects is the decrease in blood pressure which may lead to decrease in CPP in head injured patients. (14, 15, 16)

Ketamine-Propofol combination (Ketofol) is a compound formed by addition of racemic

Ketamine to Propofol in different ratio concentrations ranging from 1:1 to 1:4 (Ketamine / Propofol). It is used for procedural sedation and Analgesia, (17) as the effects of their combination on hemodynamic and respiratory systems are complementary to each other, and their side effects on these systems may be reduced by using lower doses of both drugs in such combination. (18, 19, 20) Other studies proved that ketamine-Propofol combination (ketofol) can be safely used for general anesthesia in pediatric patients undergoing cardiac catheterization and during induction in patients with coronary artery disease and left ventricular dysfunction undergoing coronary artery bypass graft surgery. (21, 22) Other studies revealed that using ketamine - Propofol mixture can be an alternative strategy to enhance the seizure quality and clinical efficiency of electroconvulsive therapy. (18, 23) Searching in literatures showed that recent uses of Ketamine - Propofol combination (ketofol) in neuroanesthesia is seldom. So this randomized controlled trial was designed to assess the effect of using Ketamine - Propofol combination as an induction agent in isolated head trauma patients on the CPP, ICP and MAP. We hypothesized that using ketofol as an induction agent in isolated head trauma patients would be beneficial in maintaining blood pressure and CPP, without increasing ICP. Material and Methods

This study was conducted at the neurosurgery operative theatre at Cairo University Hospital after approval of the Ethical and research committee of the Anesthesiology department in Cairo University. A written informed consent obtained from the patients' relatives, forty patients with isolated head trauma and candidates for craniotomy procedures were included in this study.

Omar Waguih Abbas et al

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Patients of both sex, aged 20 – 50 years, ASA I & II, with traumatic brain injuries (CT findings of extradural hematoma, compound depressed fracture, chronic subdural hematoma), and with Glascow coma scale (GCS) 13 were included in the study. Patients with polytrauma, hemorrhagic shock, hydrocephalus and were excluded from the study. Any intraoperative major events (massive bleeding requiring blood transfusion, use of inotropes or any episode of air embolism) as well as patients receiving anticoagulant drugs were also excluded from the study; as these conditions will be associated with variations in hemodynamics (specially blood pressure) and subsequently mean arterial pressure (MAP) and CPP.

On arrival to OR each of the 40 patients were randomly allocated in 1 of 2 groups (20 patients each), using computerized random number concealed in closed sealed opaque envelope. Group (K) received Ketamine- Propofol combination (ketofol) and group (P) received Propofol as an induction agent for anesthesia. Full monitoring applied; 5-leads ECG, invasive blood pressure and pulse oximetry and peripheral nerve stimulator before induction of general anesthesia. Core temperature monitoring by a nasopharyngeal probe, capnography, and indwelling urinary catheter for hourly urine output were applied after induction of anesthesia.

Before induction of GA, the ICP monitoring probe (Codman Micro Sensor, Johnson & Johnson Medical Ltd) was inserted by the surgeon into the contra lateral side of surgery at Kocher's point (located 2 to 3 cm lateral to midline and 1 cm anterior to the coronal suture). ICP probe was inserted using local anesthesia 5 ml lidocaine 2% after sterilization of initial access hole and proper draping. A burr hole was created through which the Codman micro sensor was placed and inserted into deep white matter, at a depth of 20- 35mm from the cortical surface and ICP baseline value was recorded. ICP

measurements were also used to estimate baseline cerebral perfusion pressure as follows:

Mean CPP = Mean arterial blood pressure (MAP) – Mean ICP.

In Group K, Induction was started using intravenous injection of ketofol at a concentration of (1:1). It was prepared by adding 10ml of 10% Propofol (100 mg) plus 2 ml racemic Ketamine (100 mg) plus 8 ml glucose 5% to form a solution of 20ml. Each 1 ml of this prepared solution contains 5 mg Ketamine and 5 mg Propofol, the induction dose of this mixture was 0.2 ml/kg (which is equivalent to 1mg/kg Propofol plus 1 mg/kg ketamine) and it was given slowly over 30 seconds. In Group (P), induction was started with 10% Propofol solution with dose of 0.2 ml / kg (which is equivalent to 2 mg/kg) slowly over 30 seconds. The induction of GA in both groups was accomplished using Rocuronium (0.9 mg/kg), Fentanyl 2 µg/kg & Lidocaine 1.5 mg/kg one minute before intubation. Anesthesia was maintained by Isoflurane (1-1.5% end tidal concentration) in Oxygen and rocuronium infusion (5-10 µg/kg/minute). Patients were mechanically ventilated to achieve a PaCO2 between 30-35mmHg. Maintenance Intravenous fluids were given in the form of crystalloids (3ml/kg/h).

At the end of the surgery, inhalational anesthetic was discontinued and muscle relaxant effect reversed with neostigmine (0.05 mg/kg) and atropine (0.02 mg/kg). After regaining conscious level, patients were extubated and transferred to PACU.

Our aim was investigate if ketofol combination can decrease ICP while maintaining CPP in head trauma in comparison to propofol whish was expected to decrease both ICP and CPP Data collected: Mean arterial blood pressure (MAP), heart rate HR, intracranial pressure ICP and cerebral perfusion pressure CPP were recorded at the

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following time interval: base line (before induction of GA), at induction of anesthesia, 2 and 4 minutes after induction. Then at intubation, 2 and 4 minutes after intubation, at skin incision, at dural opening, then every 5 min for three readings after dural opening and at dural closure. Time from discontinuation of inhalational anesthetics till extubation (extubation time) and time interval from discontinuation of inhalational anesthetics till obeying orders (time to obey orders) were also recorded. Complications nausea, vomiting were documented. Statistical analysis: Collected data were expressed as means (± SD), median (range) or number (%) of patients as appropriate. Continuous data were compared by two-way ANOVA or repeated measures ANOVA with Dunnett's test as a post-hoc procedure for comparisons against baseline values to further investigate any statistically significant findings. Indices were analyzed using Chi-squared test or Fisher's exact test where appropriate. Statistical calculations were performed using SPSS (Version 15, 2006) statistical package. Results were considered statistically significant if P value < 0.05. Sample size calculated using data from previous study (39) that measured ICP in patient on Propofol sedation and received different ketamine doses. ICP was 15 +- 8 5 minutes after 1.5 /kg mg ketamine. By assuming 20% decrease with Propofol alone. A power of 90% and alpha error of 0.05 were admitted to G power software (3.1.3 version). Sample size was 13 patients in each group which rolled up to 20 in each group. Results There were no statistically significant differences between the study groups as regard patient’s demographic and neurological data. (Table 1)

Relative to baseline, the ICP decreased

significantly after induction of anesthesia till endotracheal intubation in both study arms. At intubation, patients in ketofol group, showed significant elevation of ICP compared to baseline with P value > 0.05 then declined again significantly. (Table-2)

Comparing Measured ICP values between both groups, the Propofol group showed lower ICP values compared to Ketofol group starting from induction till Dural opening with P values < 0.05. After Dural opening, there was no statistical significant differences in measured ICP values between both groups. (Table-2)

Comparing MAP readings at different points of measurement to baseline values in Ketofol group, the MAP showed statistically significant increase starting from intubation till after skin incision (P<0.05). Then after Dural opening the MAP showed statistically significant decrease till Dural closure with P<0.05. On the other hand values measured in Propofol when compared to baseline value in the same group, the MAP showed statistically significant decrease starting at induction, 2 and 4 min after induction with (P< 0.05), it then showed statistically significant increase at 2 points; one min after intubation and one min after skin incision with (P<0.05), then after Dural opening, MAP started to decrease again till Dural closure with (P< 0.05). Figure1

By comparing MAP values between both groups, MAP in group P was statistically significantly lower than group K starting from induction till intubation with p values (P< 0.05). From skin incision till the end of the procedure there was no statistical significance between both groups. (Figure1)

As regard the heart rate (HR); in Ketofol group, HR showed statistically significant increase starting from intubation till dural opening with (P<0.05). IN Propofol group; HR showed statistically significant decrease from induction, 2 & 4 min after induction with (P< 0.05), then statistically significant increase

Omar Waguih Abbas et al

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from one min after intubation till Dural opening with p value (P<0.05). (Figure 2)

By comparing HR values in group P with group K, HR was statistically lower in group P starting from induction till skin incision with p value of (P< 0.05). After skin incision, no statistically significant difference detected between the 2 groups. (Figure 2)

While evaluating CPP values within the same group compared to the baseline values; Group K showed a statistically significant increase in CPP in all readings starting from induction till Dural closure with P< 0.05. In group P, CPP showed a statistically significant increase relative to baseline after intubation till Dural closure with P< 0.05. (Table 3)

By comparing the CPP values between the two groups P and K, it was obvious that the measured CPP values in group P was significantly lower than group K starting from induction till intubation (P < 0.05), while the CPP showed a significant increase in group P at skin incision (P< 0.05). (Figure 3)

There were no statistically significant differences between both groups in extubation time nor time to obey orders. (Table 4)

As for the incidence of occurrence of complications; Post-operative nausea and vomiting, the antiemetic effects of Propofol were evident in the ketofol group as no patient suffered from nausea or vomiting.

Discussion:

The main finding of our study is that ketofol is a safe agent for induction anesthesia in patients with isolated TBI. Ketofol can decrease the ICP and at the same time maintains the CPP.

The main challenge when dealing with patients with traumatic brain injury is to prevent secondary brain insult which may be caused by elevated intracranial pressure, decreased CPP,

hypoxia, hypercapnia and systemic hypotension.

In our study comparing ICP in both groups, ICP showed statistically significant decrease in both groups in relation to baseline values. These results coincide with the results of Bar-Joseph G, and his colleagues. They studied the effect of ketamine administration as a single dose (1–1.5 mg/kg) in 30 sedated, mechanically ventilated pediatric head trauma patients with intracranial hypertension in intensive care unit and they found that; ketamine effectively decreased ICP and prevented ICP elevations during potentially distressing interventions, without lowering blood pressure and CPP. (24) Another study by Bourgoin A et al, who compared continuous infusion of ketamine-Midazolam versus continuous infusion of Sufentanil-midazolam in sedation of mechanically ventilated adult patients with severe head trauma and they found no significant differences in the mean daily values of ICP and CPP or in the number of ICP elevations between both groups. (25) Similarly, Kolend et al, compared ketamine/Midazolam sedation with Fentanyl/Midazolam sedation in patients with moderate to severe TBI and found a non-significant 2mmHg higher ICP values, less doses of catecholamines required, and CPP readings were only higher in the ketamine/ midazolam group. (26)

Mayberg and his colleagues (ref) studied the effect of ketamine administration on 20 patients undergoing craniotomy procedures and they found that after induction of anesthesia with thiopental and maintenance of anesthesia with isoflurane and nitrous oxide then after stabilization of hemodynamics (around 15 min from induction), an intravenous bolus of ketamine (1 mg/kg) was given, the CPP was maintained and they concluded that ketamine can be used in anesthetized patients, when mechanically ventilated with only mild increase in ICP without adversely altering cerebral

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hemodynamics including middle cerebral artery blood flow velocity, CPP ,MAP. (27)

In contrast to our study, Cumarine RS and his colleagues studied the effect of ketamine administration on 26 hydrocephalic children and they found that there was marked increase in ICP with ketamine administration.(28) Also Gardner and his colleagues studied the effect of ketamine administration as 2mg|kg on 11healthy patients candidates for procedures using spinal anesthesia and they found that there were marked increase in ICP with ketamine administration.(29) ) those result could be explained by the fact that Almost all of these ICP elevations were observed in patients who were breathing spontaneously, although most of the reports stressed that the patients continued to breathe effectively and the PaCO2 did not increase, and it should be mentioned that ICP raised when ketamine was received as a sole anesthetic agent. In our study there was statistically significant decrease in ICP reading in the Propofol group greater than ketofol group. In line with our study, Sankari Santra and his colleagues (30) examined 68 patients undergoing craniotomy for supratentorial tumors. They concluded that during craniotomy for supratentorial cerebral tumors, subdural measured ICP was lower in patients anaesthetized with Propofol than combination of Isoflurane-nitrous oxide. After hyperventilation, there were no significant difference of ICP measurements and dural tension. (30) Also Petersen KD, and his colleagues examined 117 patients subjected to elective craniotomy for supratentorial tumor they compared the effect of Propofol, Isoflurane,and Sevoflurane on ICP measurement (they divided the patients into 3 groups; Propofol: N = 41; Isoflurane: N = 38; Sevoflurane: N = 38). Nitrous oxide was omitted and all patients were supplemented with a continuous infusion of Fentanyl. ICP was measured subdural after removal of the bone flap and

they found that; ICP was significantly lower in the Propofol group compared to the Isoflurane and Sevoflurane groups. (31) In contrast to our, Van Hemelrijck J. They examined 7 patients with a brain tumor and increased ICP. They were treated by ventriculo-subcutaneous drainage and the intracranial pressure and cerebral perfusion pressure were continuously monitored and documented. During induction of anesthesia Intracranial pressure did not change significantly before intubation, Cerebral perfusion pressure decreased before intubation, but did not differ from the baseline during and after intubation. It is concluded that Propofol 2.5 mg/kg in a bolus injection does not decrease ICP but can produce a significant decrease of the cerebral perfusion pressure due to a marked decrease in mean arterial pressure in patients with a brain tumor (32), this can be explained by the higher doses of propofol used in induction. There was no decrease in ICP in this study as probably due to small number of patients examined. Our study results as regard MAP and HR showed hemodynamic stability in patients of Ketofol group in contrast to Propofol group starting from induction till intubation. The later showed hypotension and bradycardia after induction. This is explained by the fact that Propofol causes reduction in systemic vascular resistance, cardiac contractility and preload, while ketamine in the ketofol mixture have a sympathetic stimulant which was counterbalanced by the effect of Propofol. These results coincide with the results of Arora et al. (33) who studied 10 adult patients (over age 18) for procedural sedation given ketofol in1:1 ratio and proved the hemodynamic stability of this mixture. Also, Akin et al. (34)

who found hemodynamic stability of ketofol in children undergoing cardiac catheterization. This is also consistent with the result of HUI. et al. Who found improved cardiovascular stability when using different mixtures of Propofol and ketamine in comparison to either

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drugs used solely. (35) Also, Erdogan MA and his colleagues who found improved cardiovascular stability when using different mixtures of Propofol and ketamine in ketofol (1:1) versus Propofol as induction agent before LMA airway insertion in 80 elderly patients. (36) Also, Smischney NJ and his colleagues compared the effect of ketofol versus Propofol as induction agent before GA and they found that Propofol generates a 20% reduction in systolic blood pressure from baseline at 5 minutes and 10 minutes while use of Ketofol is associated with improved hemodynamic stability during the first 10 minutes after induction. (37) Also, Saban Yalcin and his colleagues compared the effect of ketofol versus Propofol and ketamine as induction agent before electroconvulsive therapy and they found that Propfol caused decrease in hemodynamics while ketamine increased the hemodynamics and ketofol (1:1) maintained hemodynamics after induction in 90 patients undergoing ECT. (23) In contrast to our study, Daniel J and his colleagues, compared the effect of ketofol (1:2) versus Propofol as an induction agent on hemodynamics in 85 healthy patients scheduled for surgery, they found a significant decrease in systolic blood pressure of >20% from baseline in both groups; more in Propofol than ketofol group at 5 minutes and at10 minutes. No significant difference was noted at 30 minutes. (38) This result may be due to using ketofol (1:2) which contains more Propofol doses which is responsible for hypotension while in ketofol (1:1) used in previously mentioned studies showed hemodynamic stability. While evaluating CPP in our study; Group K (ketofol) showed significant increase in CPP relative to baseline starting from induction till dural closure. While Group P (Propofol) showed significant increased CPP relative to baseline only after intubation till dural closure. The CPP values in Propofol group was lower than ketofol group starting from induction till intubation.

In line with our results; Albenase and his colleagues studied the effect of ketamine administration at 3 different doses (1.5, 3, and 5 mg/ kg) during Propofol sedation in 8 head trauma patients while they were mechanically ventilated and they found that there was significant decrease in ICP at the 3 doses of ketamine and there were no statistical significant difference in CPP, middle cerebral artery blood flow velocity, jugular vein bulb oxygen saturation. They concluded that ketamine-Propofol may not adversely alter cerebral hemodynamics of mechanically ventilated head trauma patients. 39)Also Kazuyuki Sakai and his colleagues studied the effects of ketamine-Propofol anesthesia on cerebral circulation by using transcranial Doppler ultrasonography, they found that this combination did not influence middle cerebral artery blood flow velocity or the cerebrovascular CO2 response assessed by transcranial Doppler ultrasonography in patients without neurological complications. (40) They explained their results as the ketamine will not increase ICP due to controlled ventilation that will prevent hypercarbia, and this combination blunts CNS excitation and increases the depth of anesthesia. As regard recovery times (time to obeying orders and time to extubation) there were no statistical significant differences between both groups. This could be explained as the effect of both drugs had been eliminated at the end of the procedure. In contrast with our results; Saban Yalcin and his colleagues compared the effect of ketofol (1:1) mixture versus Propofol and ketamine as induction agent before electroconvulsive therapy and they found that recovery time of ketofol is longer than Propofol and shorter than ketamine. (23) Also Gary Andolfatto and his colleagues studied the effect of Ketofol (1:1) mixture as PSA (procedural sedation and analgesia) in 728 patients for primarily orthopedic procedures they found that rapid recovery time with ketofol which is longer

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than Propofol and shorter than ketamine. (41)Also Paulo Sérgio Lucas da Silva and his colleagues studied the effect of ketofol (1:1) in 20 patients aged between 4 and 12 years requiring sedation for bone marrow aspiration And they found that the median recovery time was 23 min (42) They explained their results as the use of ketamine and Propofol in combination might be decreasing recovery time than ketamine alone by reducing the total amount of ketamine but still the recovery time is longer than Propofol alone. This study used general concepts in assessing of ketofol effect on ICP and CPP in traumatic brain injury. Further studies are needed to assess this combination in patients with already elevated ICP with low GCS or who are hemodynamically unstable in different age groups. Conclusion: Ketofol (1:1) combination is a safe, effective alternative induction agent in isolated head trauma patient as it decreased ICP and preserved ABP; thus, it provided a better CPP compared to propofol, with no effect on recovery time and it lacks many side effects of its two components if used seperatly.

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26. Kolenda H, Gremmelt A, Rading S, et al. Ketamine for analgosedative therapy in intensive care treatment of head-injured patients. Acta Neurochir (Wien) 1996; 138:1193–1199.

27. Mayberg T S , Lam A M, Matta B F et al .. . Ketamine does not increase cerebral blood flow velocity or Intra cranial pressure during isoflorane / Nirous Oxid anthesthesia in patients undergoing craniotomy. Anthesthesia analgesia 1995;81:84-89.

28. Crumrine RS, Nulsen FE, Weiss MH. Alterations in ventricular fluid pressure during ketamine anesthesia in hydrocephalic children. Anesthesiology 1975;42:758–761.

29. Gardner AE, Olson BE, Lichtiger M. Cerebrospinal fluid during dissociative

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30. SantraS, Das B. Subdural Pressure and Brain Condition During Propofol Vs Isoflurane - Nitrous Oxide Anaesthesia in Patients Undergoing Elective Supratentorial Tumour Surgery .Indian J Anaesth. 2009 February; 53(1): 44–51.

31. Petersen KD, Landsfeldt U, Cold GE, et al.ICP is lower during propofol anaesthesia compared to isoflurane and sevoflurane. Acta Neurochir Suppl. 2002;81:89-91.

32. Van Hemelrijck J, Van Aken H, Plets C, et al.The effects of propofol on intracranial pressure and cerebral perfusion pressure in patients with brain tumors. Acta Anaesthesiol Belg 1989;40(2):95-100.

33. Arora S, Martin CL, Fernandez MM,et al. Combining ketamine and propofol (ketofol) for emergency sedation in emergency department. Ann Emerg Med 2007;50(3):121.

34. Akin A, Esmaoglu A, Guler G, et al. Propofol and propofol ketamine in pediatric patients undergoing cardiac catheterization. Pediatr Cardiol 2005;26:553–7.

35. Hui TW, Short TG, Hong W, et al. Additive interactions between propofol and ketamine when used for anesthesia induction in female patients. Anesthesiology 1995;82:641–8.

36. Erdogan MA , Begec Z, Aydogan M S, et al. Comparison of effects of propofol and ketamine–propofol mixture(ketofol) on laryngeal mask airway insertion conditions and hemodynamics in elderly patients: a randomized,prospective, double-blind trial. J Anesth August 2012; 1484-5.

37. Smischney NJ, Beach ML, Loftus RW, et al.Ketamine/propofol admixture (ketofol) is associated with improved hemodynamics as an induction agent: a randomized, controlled trial.J Trauma Acute Care Surg 2012 Jul;73(1):94-101.

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Table (1): demographic data

Group A (ketofol) (n=20)

Group B (propofol) (n=20)

Age (years) 39.3±2.3 41.1±1.9

Gender (M:F) 11:9 13:7

Body weight (Kg) 62.3±3.2 65.1±3.9

Body height (cm) 166.3±2.3 168.9±2.2

Body mass index (Kg/m2)

22.7±0.63 23.4±1.1

Hypertension 3 2

Ischemic changes in ECG 1 0

Diabetes 1 2

ASA grade I 15 16

II 5 4

Extradural he 8 8

Compound depressed fracture

7 6

Subdural he 5 6 *: significant difference between study groups (P < 0.05)

Table (2) comparison between both groups (ketofol and Propofol) and between each group and the baseline as regard ICP

ICP Group Ketofol Group Propofol

base line 16.95±3.33 16.60±1.67

Induction 15.60±3.38† 13.00±1.41*†

2 min after induction

15.00±2.92† 12.55±1.43 *†

4 min after induction

15.45±2.80† 12.50±1.28 *†

Intubation 18.95±3.83† 16.20±1.54*

2 min after intubation

17.10±2.63 15.25±1.48*†

4 min after intubation

15.90±2.51† 14.10±1.29*†

skin incision 15.30±2.45† 13.20±1.06*†

dural opening 14.50±2.50† 12.55±1.19 *†

5 min later 13.65±2.16† 12.70±1.08†

5 min later 13.05±2.35† 12.05±1.19 †

5 min later 12.20±1.99† 11.30±1.03†

dural closure 11.35±2.18† 10.71±1.26†

*Means statistically significance between both groups (P< 0.05) † Means statistically significance between each reading and the baseline reading in each groups(P< 0.05

Figure (1) comparison between both groups (ketofol and propofol) and between each group and the baseline as regard MAP.

75

80

85

90

95

100

105

base

line

indu

ction

2 m

in aft

er in

ducti

on

4 m

in aft

er in

ducti

on

intub

ation

2m

in aft

er in

tuba

tion

4 m

in aft

er in

tuba

tion

skin

incisi

on

dural

opnin

g

5 m

in lat

er

5 m

in lat

er

5 m

in lat

er

dural

clos

ure

MAP

ketofol propofol

*Means statistically significance between both groups (P< 0.05) † Means statistically significance between each reading and the baseline reading in each groups(P< 0.05)

Figure (2) comparison between both groups (ketofol and propofol) and between each group and the baseline as regard HR.

* Means statistically significance between both groups(P< 0.05) † Means statistically significance between each reading and the baseline reading in each groups(P< 0.05)

60

65

70

75

80

85

90

base

line

indu

ction

2 min

after

indu

ction

4 min

after

indu

ction

intub

ation

2 min

after

intu

batio

n

4 min

after

intu

batio

n

skin

incisi

on

dural

opnin

g

5 m

in lat

er

5 m

in lat

er

5 min

later

dural

clos

ure

HR

Ketofol Propofol

EJICT 2018, Vol. 8 No. (2) September

23

Table 3 comparison between both groups (ketofol and Propofol) and between each group and the baseline as regard CPP.

CPP Ketofol Group Propofol Group

base line 73.80±2.69 73.80±2.44

Induction 75.50±3.41† 73.55±2.33*

2min after induction 76.40±3.50† 73.50±2.87*

4min after induction 75.80±3.64† 73.65±2.25*

Intubation 76.60±4.45† 75.30±3.08†

2min after intubation

77.05±4.03† 75.65±2.76†

4min after intubation

77.25±4.02† 75.80±2.86†

skin incision 76.40±3.50† 78.75±2.17*†

dural opning 76.20±4.14† 76.60±2.89†

5 min later 76.00±3.89† 76.15±1.66†

5 min later 76.85±4.36† 76.35±1.8†

5 min later 77.40±4.49† 76.65 ±1.86†

dural closure 77.41±4.21† 77.05±1.69†

* Means statistically significance between both groups(P< 0.05) † Means statistically significance between each reading and the baseline reading in each groups(P< 0.05)

Figure (3) comparison between both groups (ketofol and propofol) and between each group and the baseline as regard CPP.

*Means statistically significance between both groups (P< 0.05) † Means statistically significance between each reading and the baseline reading in each groups(P< 0.05)

Table 4 comparison between both groups as regard recovery time. Ketofol

Group

Propofol

group

Min Min

Time to obeying 4.00±.00 3.95±.22

Time to

extubation

4.45±.25 4.21±.47

* Means statistically significance between both groups

(P< 0.05

Ketofol propofol

60

65

70

75

80

85

90

base

line

indu

ction

2 min

after

induc

tion

4 min

after

induc

tion

intub

ation

2 min

after

intub

ation

4 min

after

intub

ation

skin i

ncisio

n

dural

opnin

g

5 min

later

5 min

later

5 min

later

dural

closu

re

HR

Ketofol Propofol

60

65

70

75

80

85

90

base line

induction

2 min after induction

4 min after induction

intubation

2 min after intubation

4 min after intubation

skin incision

dural opning

5 min later

5 min later

5 min later

dural closure

HR

Ketofol Propofol

70

72

74

76

78

80

82

base

line

indu

ction

2 min

after

induc

tion

4 min

after

induc

tion

intub

ation

2 min

after

intub

ation

4 m

in aft

er int

ubati

on

skin i

ncisio

n

dural

opnin

g

5 min

later

5 min

later

5 min

later

dural

closu

re

CPP

Ketofol Propofol

70

72

74

76

78

80

82

base line

induction

2 min after induction

4 min after induction

intubation

2 min after intubation

4 min after in

tubation

skin incision

dural opning

5 min later

5 min later

5 min later

dural closure

CPP

Ketofol Propofol

70

72

74

76

78

80

82

base

line

indu

ction

2 min

after

induc

tion

4 min

after

induc

tion

intub

ation

2 min

after

intub

ation

4 m

in aft

er int

ubati

on

skin i

ncisio

n

dural

opnin

g

5 min

later

5 min

later

5 min

later

dural

closu

re

CPP

Ketofol Propofol