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A Yli-Hankala

Publications and source records attributed to A Yli-Hankala.

At least 37 records · Page 2Linked to original sources
PubMed2000

Neurophysiology of anaesthesia.

Methods of clinical neurophysiology are important in studying basic problems of anaesthesia such as the problem of the depth of anaesthesia, Some of the problems of clinical neurophysiology in awake subjects, such as the generators of somatosensory evoked potentials or cognitive evoked potentials, may be resolved by recording during EEG suppression. Finally, the mechanisms by which some anaesthetics produce epileptic phenomena (others or even the same agents may suppress epileptic activity) can only be resolved by EEG and EP recordings in human subjects, and by simultaneous recordings of intracellular and extracellular potentials in animals.

Anesthesia↗
PubMed1999

Midazolam premedication delays recovery from propofol-induced sevoflurane anesthesia in children 1-3 yr.

PURPOSE: To study the effect of midazolam premedication on the recovery characteristics of sevoflurane anesthesia induced with propofol in pediatric outpatients. METHODS: Sixty children, one to three years, presenting for ambulatory adenoidectomy were randomly assigned , in a double-blind fashion, to receive either 0.5 mg x kg(-1) midazolam (Group M) or placebo (Group P) p.o. 30 min before anesthesia. Anesthesia was induced with 10 microg x kg(-1) atropine, 10 microg x kg(-1) alfentanil, and 3-4 mg x kg(-1) propofol i.v.. Tracheal intubation was facilitated with 0.2 mg x kg(-1) mivacurium. Anesthesia was maintained with nitrous oxide/oxygen (FiO2 0.3) and sevoflurane with controlled ventilation. Recovery characteristics were compared using the modified Aldrete scoring system, the Pain/Discomfort scale and measuring specific recovery end-points (emergence, full Aldrete score, discharge). A postoperative questionnaire was used to evaluate the children's well-being at home until 24 hr after discharge. RESULTS: Emergence from anesthesia (22 +/- 9 vs 16 +/- 6 min (mean +/- SD), P = 0.005) and achieving full Aldrete scores (30 +/- 11 vs 24 +/- 16 min, P = 0.006) were delayed in patients receiving midazolam. Children in the placebo group were given postoperative analgesia sooner than those in the midazolam group (18 +/- 11 vs 23 +/- 8 min, P = 0.009). More children premedicated with midazolam suffered from arousal distress (20% vs 3%, P = 0.04) and scored higher on the Pain/Discomfort scale (P = 0.004) at 20 min after arrival in the recovery room. Discharge was not affected by premedication and well-being at home was similar in the groups. CONCLUSIONS: Oral premedication with midazolam delays early recovery but not discharge after ambulatory sevoflurane anesthesia induced with propofol in children one to three years. Midazolam did not improve the quality of recovery.

Adenoidectomy↗
PubMed1999

EEG bispectral index monitoring in sevoflurane or propofol anaesthesia: analysis of direct costs and immediate recovery.

BACKGROUND: Recent studies have suggested that electroencephalogram (EEG) bispectral index (BIS) monitoring can improve recovery after anaesthesia and save money by shortening patients' postoperative stay. We wanted to evaluate the direct costs of BIS monitoring and to measure immediate recovery after anaesthesia in patients with or without BIS monitoring. METHODS: Eighty patients undergoing gynaecological surgery were studied. At first, 40 patients were randomized to receive either propofol or sevoflurane anaesthesia. In these patients, BIS was collected but the information was not displayed. Thereafter, the anaesthesiologists were trained to follow and understand the BIS information, and 40 patients were anaesthetized with aid of the monitoring. Recovery times were measured by a study coordinator. Drug consumption was calculated. RESULTS: BIS monitoring improved the immediate recovery after propofol anaesthesia, while no differences were seen in patients receiving sevoflurane. The consumption of both propofol and sevoflurane decreased significantly (29% and 40%, respectively). BIS monitoring increased direct costs in these patients; the break-even times (704 min for propofol and 282 min for sevoflurane) were not reached. CONCLUSION: BIS monitoring decreased the consumption of both propofol and sevoflurane and hastened the immediate recovery after propofol anaesthesia. Detailed cost analysis showed that the monitoring increased direct costs of anaesthesia treatment in these patients, mainly due to the price of special EEG electrodes used for relatively short anaesthesias.

Adult↗
PubMed1999

Warming of insufflation gas during laparoscopic hysterectomy: effect on body temperature and the autonomic nervous system.

BACKGROUND: Hypothermia is a known side effect of laparoscopic operations. It may increase the sympathetic activity of the autonomic nervous system (ANS), which can be evaluated noninvasively by heart rate variability (HRV). We tested the hypothesis that warming of the delivered CO2 insufflation gas helps to maintain the normal body temperature. METHODS: Thirty-seven healthy women undergoing laparoscopic hysterectomy were randomized into heated (37 degrees C, n=18) or unheated (24 degrees C, n = 19) gas insufflation groups. Anesthesia was induced with propofol and maintained with sevoflurane in O2-air. Tympanic (ttymp) temperature was recorded before, during and after the operation. Nasopharyngeal (tnaso) temperature was recorded only during operation. Electrocardiograms were recorded and stored to evaluate changes in HRV. The individual changes in HRV were compared after decibel (dB) transformation. RESULTS: A median decrease in tympanic temperatures during the operation was 0.7 degrees C in the heated and 0.3 degrees C in the unheated group (P = 0.01 between groups), and in nasopharyngeal 0.3 degrees C and 0.1 degrees C (P = 0.03), respectively. Preanesthetic tympanic values were reached within 90 min after anesthesia. After dB transformation, HRV high frequency power differed between the groups. It was better preserved in the patients receiving unheated gas. CONCLUSION: The heating of insufflation gas does not prevent a decrease in body temperature and is thus unnecessary during laparoscopic hysterectomy.

Adult↗
PubMed1999

Sevoflurane requirement for laparoscopic tubal ligation: an electroencephalographic bispectral study.

It has been shown in healthy volunteers that a concentration of volatile anaesthetic lower than 1 minimum alveolar concentration provides unconsciousness. We tested the hypothesis that, using the electroencephalogram bispectral index, less than 1 minimum alveolar concentration of sevoflurane can produce unconsciousness in patients. Anaesthesia was induced and maintained with sevoflurane in N2O and O2 (33%) in 32 ASA I-II women undergoing laparoscopic tubal ligation. For the first patient, the sevoflurane concentration was adjusted to 1 minimum alveolar concentration with an end-tidal concentration of 0.7%. The electroencephalogram bispectral index values were used to determine the concentration to be used for the next patient. The ED50 (effective dose) measured using end tidal concentrations of sevoflurane for laparoscopic tubal ligation in a 40-year-old patient was 0.70% (CI 95%: 0.63-0.77) and ED95 0.83% (CI 95%: 0.75-0.90). None of the patients had any operation-associated recall. It is concluded that the sevoflurane concentration needed for laparoscopic tubal ligation is not lower than 1 minimum alveolar concentration.

Adult↗
PubMed1999

Comparison of sevoflurane-nitrous oxide and propofol-alfentanil-nitrous oxide anaesthesia for minor gynaecological surgery.

We studied 44 patients undergoing minor gynaecological surgery, anaesthetized in random order with sevoflurane-nitrous oxide or propofol-alfentanil-nitrous oxide. Operating conditions, recovery and postoperative nausea and vomiting (PONV) were assessed. For postoperative analgesia, all patients were given ketoprofen 100 mg rectally at the end of anaesthesia. Patients and gynaecologists were equally satisfied with both anaesthetic techniques. Patients given propofol woke up (3.5 vs 6.5 min), became orientated (5.0 vs 7.5 min) and were able to walk (57 vs 69 min) significantly (P < 0.05) earlier than those given sevoflurane, but there were no differences in times to achieve home readiness (166 vs 149 min) or in psychomotor recovery between the two groups. Intrauterine bleeding and PONV were more common with sevoflurane (incidence of PONV 64%) than with propofol anaesthesia (incidence of PONV 5%). We conclude that propofol-alfentanil is preferable to sevoflurane in ultra-short anaesthesia for minor gynaecological surgery.

Adult↗
PubMed1999

Epileptiform electroencephalogram during mask induction of anesthesia with sevoflurane.

BACKGROUND: Sevoflurane is suggested as a suitable anesthetic agent for mask induction in adults. The authors recently found that hyperventilation during sevoflurane-nitrous oxide-oxygen mask induction is associated with cardiovascular hyperdynamic response. We tested the hypothesis that the hyperdynamic response can be explained by electroencephalography (EEG) findings. METHODS: Thirty women were randomly allocated to receive sevoflurane-nitrous oxygen-oxygen mask induction using a single-breath method, followed by either spontaneous breathing (n = 15) or controlled hyperventilation (n = 15) for 6 min. EEG was recorded. Blood pressure and heart rate were recorded at 1-min intervals. RESULTS: Epileptiform EEG activity (spikes or polyspikes) was seen in all patients with controlled hyperventilation, and in seven patients with spontaneous breathing (P < 0.01). Jerking movements were seen in three patients with controlled hyperventilation. In the controlled hyperventilation group, heart rate increased 54% from baseline at 4 min after induction (P < 0.001). Mean arterial pressure increased 17% (P < 0.05), peaking at 3 min. In the spontaneous breathing group, heart rate showed no change, and mean arterial pressure decreased by 14% (P < 0.01) at 6 min. Heart rate and mean arterial pressure differed significantly between the groups from 2 min after beginning of the induction to the end of the trial. An increase in heart rate of more than 30% from baseline always was associated with epileptiform EEG activity. CONCLUSIONS: Sevoflurane mask induction elicits epileptiform EEG patterns. These are associated with an increase in heart rate in patients with controlled hyperventilation and also during spontaneous breathing of sevoflurane.

Adult↗
PubMed1998

Respiratory compliance during laparoscopic hiatal and inguinal hernia repair.

PURPOSE: Side stream spirometry with dynamic compliance displayed as pressure-volume loops, has enabled early detection of CO2 pneumothorax during pneumoperitoneum. We compared dynamic compliance profiles of two laparoscopic procedures with different patient positions. METHODS: In 26 patients, scheduled either for laparoscopic fundoplication in a head-up tilt or inguinal herniorrhaphy in a head-down tilt, dynamic compliance was measured with continuous spirometry from anaesthesia induction until skin closure. Control pressure-volume loops were saved in the horizontal position before surgery and compared with succeeding loops in the head-up/head-down tilt before pneumoperitoneum, during pneumoperitoneum in the horizontal and the tilt position, after evacuation of pneumoperitoneum in the tilt and finally in the horizontal position. RESULTS: Pneumoperitoneum reduced compliance in both groups by 35% (P < 0.01). Head-down tilt decreased compliance by 12% before and during pneumoperitoneum (P < 0.01). Head-up tilt increased compliance by 4% before pneumoperitoneum (P < 0.05), but during pneumoperitoneum it had no effect. After evacuation of pneumoperitoneum compliance returned immediately to control in head-up tilt, but remained reduced in head-down tilt and was not at control after adopting horizontal position (P < 0.05). Difference between the groups was significant (P < 0.01) in the head-up/head-down tilt before, during and immediately after pneumoperitoneum. CONCLUSION: Both pneumoperitoneum and head-up and head-down positions had characteristic effects on dynamic compliance. Simultaneous display of sequential pressure-volume loops enabled immediate detection of changes in respiratory mechanics.

Adolescent↗
PubMed1998

Neostigmine with glycopyrrolate does not increase the incidence or severity of postoperative nausea and vomiting in outpatients undergoing gynaecological laparoscopy.

We studied 100 healthy women undergoing outpatient gynaecological laparoscopy in a randomized, double-blind and placebo-controlled study to evaluate the effect of neostigmine on postoperative nausea and vomiting (PONV). After induction of anaesthesia with propofol, anaesthesia was maintained with sevoflurane and 66% nitrous oxide in oxygen. Mivacurium was used for neuromuscular block. At the end of anaesthesia, neostigmine 2.0 mg and glycopyrrolate 0.4 mg, or saline, was given i.v. The incidence of PONV was evaluated in the postanaesthesia care unit, on the ward and at home. The severity of nausea and vomiting, worst pain, antiemetic and analgesic use, times to urinary voiding and home readiness were recorded. During the first 24 h after operation, 44% of patients in the neostigmine group and 43% in the saline group did not have PONV. We conclude that neostigmine with glycopyrrolate did not increase the occurrence of PONV in this patient group.

Adult↗
PubMed1997

Cigarette smoking does not affect thiopentone pharmacodynamic or pharmacokinetic behaviour.

PURPOSE: Smoking affects the pharmacodynamic and pharmacokinetic behaviour of several drugs. In smokers, induction of anaesthesia is often stormy. In this study we have determined whether cigarette smoking affected thiopentone pharmacodynamic or pharmacokinetic behaviour curing induction of anaesthesia. METHODS: Fifteen smokers and 15 non-smokers, scheduled for elective surgery, were studied. Heart rate, invasive arterial pressures and middle latency auditory evoked potentials were recorded awake and during thiopentone induction (9 mg.kg-1 lean body mass), before and after tracheal intubation. Blood was sampled up to 24 hr after induction to measure thiopentone plasma concentrations and to calculate pharmacokinetic parameters. RESULTS: Anaesthesia was adequate in all patients, although haemodynamic intubation response was not blunted. Latencies or amplitudes of middle latency auditory evoked potentials (MLAEP) did not differ between the groups. The postintubation latencies of Nb waves were 48.9 +/- 8.1 msec (mean +/- SD) in smokers and 48.1 +/- 8.5 msec in non-smokers. Pharmacokinetic data showed no differences between smokers and non-smokers. Clearance of thiopentone was 2.9 +/- 1.1 ml.min-1.kg-1 in smokers and 3.3 +/- 1.0 ml.min-1.kg-1 in non-smokers and elimination half life of thiopentone was 12.5 +/- 6.3 hr in smokers and 10.7 +/- 3.1 hr in non-smokers, respectively. The haemodynamic response after the induction dose of thiopentone and after tracheal intubation were similar in smokers and non-smokers. Mean postintubation systolic arterial pressures were 192 +/- 35 vs 189 +/- 20 mmHg and mean postintubation heart rates were 103 +/- 12 vs 102 +/- 17 beat per minute (bpm) in smokers and non-smokers, respectively. CONCLUSION: We conclude, that cigarette smoking does not affect the pharmacodynamic or pharmacokinetic behaviour of thiopentone.

Adult↗
PubMed1997

Respiratory sinus arrhythmia during anaesthesia: assessment of respiration related beat-to-beat heart rate variability analysis methods.

Beat-to-beat heart rate variability analysis is a powerful tool for the diagnosis of neuropathy. Respiration-related heart rate variability (respiratory sinus arrhythmia, RSA) reflects the function of parasympathetic nervous system during spontaneous ventilation while awake. RSA is also claimed to monitor the depth of anaesthesia. Power spectrum analysis or various averaging techniques of the heart rate variability are usually applied. The current literature, however, does not usually interpret the ground rules and limitations of the method used, and this may sometimes lead to erroneous conclusions on the data. The aim of our study was to compare and analyse critically the performance of different methods of evaluating RSA during anaesthesia and positive pressure ventilation. Power spectrum analysis, the root mean square of the successive RR-interval difference (RMSSD), and two respiration related methods, RSA index and average phase RSA, were included in the comparison. To test these methods, 11 patients were anaesthetised with isoflurane and their lungs were ventilated mechanically with a frequency of 6 cycles min-1. Each patient received a bolus dose of atropine (20 micrograms kg-1) during the trial. Electrocardiogram, electroencephalogram and tracheal pressure signal from respirator were recorded and analyses were performed off-line. We demonstrated that general indices, such as RMSSD, may be strongly affected by heart rate level and other non-respiration related variations in heart rate. We also showed that the effect of unwanted fluctuations on RSA can be reduced with respiration dependent beat-to-beat methods. Furthermore we confirmed that in addition to the amplitude, also the pattern of respiratory sinus arrhythmia is of interest: the pattern is reversed in phase compared to spontaneous breathing while awake, as we have shown earlier. To analyse RSA during anaesthesia, we recommend the use of an average phase RSA method based on beat-to-beat variability that shows both the amplitude and pattern of RSA. Finally, no measure of RSA should be used without a presentation of the actual beat-to-beat heart rate curve.

Adjuvants, Anesthesia↗
PubMed1997

Reversal of neuromuscular blockade with neostigmine has no effect on the incidence or severity of postoperative nausea and vomiting.

UNLABELLED: We performed this randomized, double-blind, placebo-controlled study to determine whether reversal of neuromuscular block with neostigmine increases the incidence and severity of postoperative nausea and vomiting (PONV). We studied 162 women undergoing abdominal hysterectomy and randomly allocated them into two groups. In Group A, neuromuscular block produced with mivacurium was antagonized with neostigmine 2.0 mg and glycopyrrolate 0.4 mg intravenously, whereas Group B received no drugs to facilitate antagonism of blockade. The incidence and severity of PONV was assessed up to 27 h after the operation. There was no difference in PONV between the groups (in Group A 35% had nausea and 33% vomited; in Group B 28% nauseated and 40% vomited) or in the amount of antiemetics given. We had a 75% chance to find a 30% difference in PONV. We conclude that the administration of neostigmine and glycopyrrolate at the end of anesthesia to reverse neuromuscular block does not increase the incidence or severity of PONV. IMPLICATIONS: Neostigmine may increase postoperative nausea and vomiting. In this study, omission of reversal of neuromuscular block with neostigmine failed to decrease the incidence or severity of postoperative nausea and vomiting.

Adult↗
PubMed1997

Outcome effects of different protective hypothermia levels during cardiac arrest in rats.

BACKGROUND: Although hypothermia is widely used to protect the brain during cardiac and neurologic surgery, the optimal level of cooling has not been established. This study examined the protective effect of graded levels of surface cooling on cerebral function in rats after complete global cerebral ischemia. METHODS: Groups of ketamine-anesthetized rats (13 animals in each group) were cooled to cranial temperatures of 34, 30, 27, 24, or 22 degrees C before circulatory arrest. Also a normothermic (37 degrees C) group was tested. After cooling, an 11-min circulatory arrest was produced by atraumatic chest compression. Circulatory arrest was followed by cardiopulmonary resuscitation and rewarming without postischemic intensive care. On the fifth postinsult day, neurologic outcome was scored on a 50-point neurodeficit scale (NDS 0 = normal). The percent of ischemic pyramidal neurons in the CA1 hippocampal region was also determined. RESULTS: There were no survivors in the normothermic group. Neurologic recovery was enhanced with 30 degrees C cranial temperature, as compared to outcome in the 34 degrees C group. Further cooling did not change outcome. The neurodeficit scales were significantly lower in all other groups compared to the 34 degrees C group on the fifth postinsult day. The percent of ischemic neurons did not change significantly as a function of cooling, but the lowest count appeared at 27 degrees C. CONCLUSION: In this model, moderate (30 degrees C) cooling improved neurologic outcome. There was no additional benefit from more extreme hypothermia.

Animals↗
PubMed1996

The effect of laparoscopic cholecystectomy on respiratory compliance as determined by continuous spirometry.

STUDY OBJECTIVE: To evaluate the effect of pneumoperitoneum on dynamic compliance during laparoscopic cholecystectomy with continuous spirometry. DESIGN: Prospective, open clinical study with the patients serving as their own controls. SETTING: Operating room at a university hospital. PATIENTS: 11 ASA status I and II patients scheduled for elective laparoscopic cholecystectomy. INTERVENTIONS: Pneumoperitoneum up to an intraabdominal pressure of 12 mmHg was created with carbon dioxide (CO2) insufflation. Thereafter, the patients were placed in a position combining a head-up tilt with a left side down lateral tilt, for dissection of the gallbladder. Steady levels of anesthesia and neuromuscular block, as well as a constant tidal volume of ventilation, were maintained throughout the procedure. MEASUREMENTS AND MAIN RESULTS: Airway pressures and respiratory volumes were continuously measured. Compliance was calculated by dividing expiratory tidal volume by end inspiratory pressure, and was displayed as a pressure-volume loop. After the creation of pneumoperitoneum, end-inspiratory airway pressure increased by 40%, and compliance decreased by 30%. These levels remained unchanged during surgery with the patient in a head-up and left side down lateral tilt position. After release of intraabdominal pressure, inspiratory airway pressure and compliance returned to control levels. The pressure-volume loop sloped to the right and its horizontal diameter was elongated during pneumoperitoneum. The new configuration was maintained until the loop returned to the control shape after evacuation of the pneumoperitoneum. CONCLUSIONS: Increased intraabdominal pressure during laparoscopic cholecystectomy causes a significant, but fully reversible, decrease in dynamic compliance. On-line spirometry with a graphic display of the pressure-volume loop facilitates the immediate discovery of these alterations.

Adult↗
PubMed1996

Effect of smoking on dose requirements for vecuronium.

We have compared the potency of vecuronium given to 12 smokers and 12 non-smokers during propofol-alfentanil-nitrous oxide anaesthesia. After obtaining individual dose-response curves, bolus doses of vecuronium were given to maintain neuromuscular block at 90-98% for 60 min. Adductor pollicis EMG was used to monitor neuromuscular block. Mean ED95 values were 61.38 micrograms kg-1 and 47.49 micrograms kg-1 for smokers and non-smokers, respectively (P < 0.01). The dose of vecuronium to maintain 90-98% neuromuscular block was 25% higher in smokers than in non-smokers (96.80 vs 72.11 micrograms kg-1 h-1; P < 0.01). These data reflect the effects of smoking on neuromuscular block induced by vecuronium. The effect may be at the receptor level, although possible increased metabolism of vecuronium in smokers cannot be excluded.

Adult↗
PubMed1996

Cardiopulmonary bypass-induced changes in plasma concentrations of propofol and in auditory evoked potentials.

Unbound, rather than total, plasma concentrations may be related to the anaesthetic action of propofol. Therefore, we measured plasma concentrations of propofol and recorded Nb wave latencies of auditory evoked potentials (AEP) during continuous infusion of propofol in 15 patients undergoing coronary artery bypass grafting (CABG) surgery. After induction of anaesthesia with fentanyl, propofol was infused continuously at a rate of 10 mg kg-1 h-1 for 20 min, and then the rate was reduced to 3 mg kg-1 h-1. Administration of heparin before cardiopulmonary bypass (CPB) did not affect total or unbound propofol concentration. Initiation of CPB decreased mean total propofol concentration from 2.6 to 1.7 micrograms ml-1 (P < 0.01). Simultaneously, mean unbound propofol concentration remained at 0.06 micrograms ml-1 because of a slight increase in the mean free fraction of plasma propofol (from 2.3 to 3.5%; P > 0.05). During hypothermic CPB, mean total propofol concentration increased to concentrations measured before bypass (to 2.1 micrograms ml-1; P > 0.05 vs value before CPB) and the mean unbound propofol concentration was at its highest (0.07 microgram ml-1; P < 0.05 vs value before heparin). After CPB and administration of protamine, the mean total propofol concentration remained lowered (1.7 micrograms ml-1; P < 0.05 vs value before heparin) and the mean unbound propofol concentration returned to the level measured before heparin (P < 0.001 vs value during hypothermia). The latency of the Nb wave from recordings of AEP increased after induction of anaesthesia, reached its maximum during hypothermia and was prolonged during the subsequent phases of the study. The latency of the Nb wave did not correlate with total or unbound propofol concentration. We conclude that the changes in total and unbound concentrations of plasma propofol were not parallel in patients undergoing CABG. During CPB or at any other time during the CABG procedure, the unbound propofol concentration did not decrease and Nb wave latency was prolonged compared with baseline values measured after induction of anaesthesia before the start of CPB.

Adult↗
PubMed1996

Transfusion-related acute lung injury (TRALI) after fresh frozen plasma in a patient with coagulopathy.

BACKGROUND: Transfusion-related acute long injury (TRALI) is due to specific antigen-antibody reaction involving the donor's leucocyte or granulocyte antibodies towards the recipient's antigens. Aggregation in small pulmonary vessels occurs, leading to derangement of permeability. CASE HISTORY: TRALI after transfusion of four units of fresh frozen plasma (FFP) for factor V deficiency prior to elective cholecystectomy is presented. Within a few minutes after the third unit of FFP a florid pulmonary oedema developed. Hypotension and hypoxia with SpO2 83-87% at FiO2 1.0 followed. Prompt monitoring of central haemodynamics revealed a normal cardiac index without pulmonary hypertension. The operation was then conducted as planned. The bilateral pulmonary oedema resolved after 72 hours with ventilatory support. The patient recovered without complications. When tested postoperatively, the second unit of FFP contained granulocyte antibodies and the third unit contained HLA antibodies. The crossmatch of the patient's granulocytes and lymphocytes towards the two donors of the two units of FFP was positive. CONCLUSION: When TRALI is suspected the donor blood has to be tested against the recipient. Ventilatory support of the patient is continued until adequate oxygenation is reached.

Acute Disease↗